Lung Cancer

The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.

The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.

John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”

The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.

They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.

“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”

He added: “That was out of the question.”

Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”

Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.

However, there were some benefits from the change.

She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.

“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
 

Presidential symposia

Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.

He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.

However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.

Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”

On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”

One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.

The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.

The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.

“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.

“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.

This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.

“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.

The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.

Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”

He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.

Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.

Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.

This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.

“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.

“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
 

Next year

For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.

She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.

This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.

This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.

She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.

“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”

The commentators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.

The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.

John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”

The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.

They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.

“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”

He added: “That was out of the question.”

Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”

Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.

However, there were some benefits from the change.

She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.

“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
 

Presidential symposia

Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.

He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.

However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.

Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”

On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”

One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.

The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.

The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.

“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.

“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.

This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.

“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.

The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.

Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”

He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.

Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.

Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.

This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.

“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.

“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
 

Next year

For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.

She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.

This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.

This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.

She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.

“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”

The commentators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.

The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.

John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”

The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.

They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.

“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”

He added: “That was out of the question.”

Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”

Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.

However, there were some benefits from the change.

She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.

“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
 

Presidential symposia

Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.

He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.

However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.

Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”

On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”

One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.

The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.

The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.

“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.

“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.

This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.

“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.

The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.

Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”

He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.

Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.

Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.

This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.

“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.

“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
 

Next year

For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.

She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.

This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.

This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.

She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.

“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”

The commentators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.

The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.

Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.

Pralsetinib is still awaiting approval for these thyroid cancer indications.

Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.

For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.

RET fusions are found in approximately 1%-2% of patients with NSCLC.

They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.

“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.

Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.

The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.

The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.

“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.

“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.

Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.

This article first appeared on Medscape.com.

A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.

The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.

Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.

Pralsetinib is still awaiting approval for these thyroid cancer indications.

Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.

For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.

RET fusions are found in approximately 1%-2% of patients with NSCLC.

They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.

“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.

Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.

The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.

The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.

“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.

“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.

Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.

This article first appeared on Medscape.com.

A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.

The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.

Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.

Pralsetinib is still awaiting approval for these thyroid cancer indications.

Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.

For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.

RET fusions are found in approximately 1%-2% of patients with NSCLC.

They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.

“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.

Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.

The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.

The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.

“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.

“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.

Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.

This article first appeared on Medscape.com.

The first targeted therapy for patients with advanced non–small cell lung cancer (NSCLC) harboring MET mutations, capmatinib (Tabrecta), has shown deep and durable responses, conclude investigators of the pivotal trial that led to the drug’s approval.

Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.

Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.

These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.

“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.

“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.

Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.

“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”

That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.

It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.

Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.

“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”

The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.

In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.

Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.

The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.

Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”

He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
 

The future is bright

Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”

Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.

“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”

The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The first targeted therapy for patients with advanced non–small cell lung cancer (NSCLC) harboring MET mutations, capmatinib (Tabrecta), has shown deep and durable responses, conclude investigators of the pivotal trial that led to the drug’s approval.

Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.

Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.

These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.

“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.

“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.

Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.

“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”

That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.

It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.

Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.

“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”

The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.

In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.

Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.

The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.

Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”

He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
 

The future is bright

Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”

Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.

“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”

The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The first targeted therapy for patients with advanced non–small cell lung cancer (NSCLC) harboring MET mutations, capmatinib (Tabrecta), has shown deep and durable responses, conclude investigators of the pivotal trial that led to the drug’s approval.

Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.

Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.

These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.

“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.

“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.

Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.

“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”

That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.

It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.

Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.

“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”

The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.

In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.

Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.

The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.

Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”

He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
 

The future is bright

Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”

Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.

“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”

The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

COVID-19 patients with cancer have a significantly greater risk of venous thromboembolism (VTE) and sepsis, but no greater risk of death, when compared to COVID-19 patients without cancer, according to data from a registry study.

Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.

There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.

After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.

The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.

Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.

She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).

“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”

In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.

Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.

“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”

Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.

Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.

“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”

Ms. Alpert reported having no disclosures.

sworcester@mdedge.com

SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.

COVID-19 patients with cancer have a significantly greater risk of venous thromboembolism (VTE) and sepsis, but no greater risk of death, when compared to COVID-19 patients without cancer, according to data from a registry study.

Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.

There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.

After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.

The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.

Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.

She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).

“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”

In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.

Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.

“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”

Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.

Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.

“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”

Ms. Alpert reported having no disclosures.

sworcester@mdedge.com

SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.

COVID-19 patients with cancer have a significantly greater risk of venous thromboembolism (VTE) and sepsis, but no greater risk of death, when compared to COVID-19 patients without cancer, according to data from a registry study.

Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.

There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.

After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.

The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.

Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.

She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).

“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”

In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.

Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.

“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”

Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.

Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.

“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”

Ms. Alpert reported having no disclosures.

sworcester@mdedge.com

SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.

Recommendations on the use of next-generation sequencing (NGS) tests for patients with metastatic cancer have been issued by the European Society for Medical Oncology, the first recommendations of their kind to be published by any medical society.

“Until now, there were no recommendations from scientific societies on how to use this technique in daily clinical practice to profile metastatic cancers,” Fernanda Mosele, MD, medical oncologist, Gustave Roussy, Villejuif, France, said in a statement.

NGS testing is already used extensively in oncology, particularly in metastatic cancer, she noted. The technology is used to assess the sequence of DNA in genes from a tumor tissue sample. Numerous genes can be quickly sequenced at the same time at relatively low cost. The results provide information on mutations that are present, which, in turn, helps with deciding which treatments to use, including drugs targeting the identified mutations.

“Our intent is that they [the guidelines] will unify decision-making about how NGS should be used for patients with metastatic cancer,” Dr. Mosele said.

The recommendations were published online August 25 in Annals of Oncology.

Overall, ESMO recommends the use of tumor multigene NGS for non–small cell lung cancer (NSCLC), prostate cancer, ovarian cancer, and cholangiocarcinoma.

For other cancers, the authors said that NGS is not recommended in clinical practice but could be used for research purposes.

However, patients should be informed that it is unlikely that test results would benefit them much personally.

Physicians and patients may decide together to subject the tumor to mutational testing using a large panel of genes, provided testing doesn’t burden the health care system with additional costs.

“This recommendation acknowledges that a small number of patients could benefit from a drug because they have a rare mutation,” Joaquin Mateo, MD, chair of the ESMO working group, said in a statement.

“So beyond the cancers in which everyone should receive NGS, there is room for physicians and patients to discuss the pros and cons of ordering these tests,” he added.

ESMO also does not recommend the use of off-label drugs matched to any genomic alteration detected by NGS unless an access program and a decisional procedure have been developed, either regionally or nationally.
 

No need for NGS testing of other cancers

In contrast to NSCLC, “there is currently no need to perform tumor multigene NGS for patients with mBC [metastatic breast cancer] in the context of daily practice,” ESMO stated.

This is largely because somatic sequencing cannot fully substitute for germline testing for BRCA status, and other mutations, such as HER2, can be detected using immunohistochemistry (IHC).

The same can be said for patients with metastatic gastric cancer, inasmuch as detection of alterations can and should be done using cheaper testing methods, ESMO pointed out.

However, ESMO members still emphasized that it’s important to include patients with metastatic breast cancer in molecular screening programs as well as in clinical trials testing targeted agents.

Similarly, there is no need to test metastatic colorectal cancer (mCRC) using multigene NGS in daily practice, inasmuch as most level 1 alterations in mCRC can be determined by IHC or PCR.

However, NGS can be considered as an alternative to PCR-based tests in mCRC, provided NGS is not associated with additional cost.

ESMO again recommended that research centers include mCRC patients in molecular screening programs in order for them to have access to innovative clinical trial agents.

As for advanced prostate cancer, ESMO does recommend that clinicians perform NGS on tissue samples to assess the tumor’s mutational status, at least for the presence of BRCA1 and BRCA2 mutations, when patients have access to the poly (ADP-ribose) polymerase inhibitors for treatment.

The authors cautioned, however, that this strategy is unlikely to be cost-effective, so larger panels should be used only when there are specific agreements with payers.

Multigene NGS is also not recommended for patients with advanced pancreatic ductal adenocarcinoma (PDAC), although ESMO points out that it is the role of research centers to propose multigene sequencing for these patients in the context of molecular screening programs.

This is again to facilitate access to innovative drugs for these patients.

Similar to recommendations for patients with advanced PDAC, patients with advanced hepatocellular carcinoma (HCC) do not need to have tumor multigene NGS either.

Considering the high unmet needs of HCC patients, ESMO feels that research centers should propose multigene sequencing to patients with advanced HCC in the context of molecular screening programs.

In contrast, ESMO recommended that tumor multigene NGS be used to detect actionable alterations in patients with advanced cholangiocarcinoma.

Again, they predict that this strategy is unlikely to be cost-effective, so larger panels should only be used if a specific agreement is in place with payers.

ESMO also assessed the frequency of level 1 alterations in less frequent tumor types, including ovarian cancers. Because BRCA1 and BRCA2 somatic mutations in ovarian tumors have been associated with increased response to the PARP inhibitors, the use of multigene NGS is justified with this malignancy, ESMO states.

The authors also recommend that tumor mutational burden be determined in cervical cancer, moderately differentiated neuroendocrine tumors, salivary cancers, vulvar cancer, and thyroid cancers.

Dr. Mosele has disclosed no relevant financial relationships. Many coauthors have relationships with the pharmaceutical industry, as listed in the article.

This article first appeared on Medscape.com.

Recommendations on the use of next-generation sequencing (NGS) tests for patients with metastatic cancer have been issued by the European Society for Medical Oncology, the first recommendations of their kind to be published by any medical society.

“Until now, there were no recommendations from scientific societies on how to use this technique in daily clinical practice to profile metastatic cancers,” Fernanda Mosele, MD, medical oncologist, Gustave Roussy, Villejuif, France, said in a statement.

NGS testing is already used extensively in oncology, particularly in metastatic cancer, she noted. The technology is used to assess the sequence of DNA in genes from a tumor tissue sample. Numerous genes can be quickly sequenced at the same time at relatively low cost. The results provide information on mutations that are present, which, in turn, helps with deciding which treatments to use, including drugs targeting the identified mutations.

“Our intent is that they [the guidelines] will unify decision-making about how NGS should be used for patients with metastatic cancer,” Dr. Mosele said.

The recommendations were published online August 25 in Annals of Oncology.

Overall, ESMO recommends the use of tumor multigene NGS for non–small cell lung cancer (NSCLC), prostate cancer, ovarian cancer, and cholangiocarcinoma.

For other cancers, the authors said that NGS is not recommended in clinical practice but could be used for research purposes.

However, patients should be informed that it is unlikely that test results would benefit them much personally.

Physicians and patients may decide together to subject the tumor to mutational testing using a large panel of genes, provided testing doesn’t burden the health care system with additional costs.

“This recommendation acknowledges that a small number of patients could benefit from a drug because they have a rare mutation,” Joaquin Mateo, MD, chair of the ESMO working group, said in a statement.

“So beyond the cancers in which everyone should receive NGS, there is room for physicians and patients to discuss the pros and cons of ordering these tests,” he added.

ESMO also does not recommend the use of off-label drugs matched to any genomic alteration detected by NGS unless an access program and a decisional procedure have been developed, either regionally or nationally.
 

No need for NGS testing of other cancers

In contrast to NSCLC, “there is currently no need to perform tumor multigene NGS for patients with mBC [metastatic breast cancer] in the context of daily practice,” ESMO stated.

This is largely because somatic sequencing cannot fully substitute for germline testing for BRCA status, and other mutations, such as HER2, can be detected using immunohistochemistry (IHC).

The same can be said for patients with metastatic gastric cancer, inasmuch as detection of alterations can and should be done using cheaper testing methods, ESMO pointed out.

However, ESMO members still emphasized that it’s important to include patients with metastatic breast cancer in molecular screening programs as well as in clinical trials testing targeted agents.

Similarly, there is no need to test metastatic colorectal cancer (mCRC) using multigene NGS in daily practice, inasmuch as most level 1 alterations in mCRC can be determined by IHC or PCR.

However, NGS can be considered as an alternative to PCR-based tests in mCRC, provided NGS is not associated with additional cost.

ESMO again recommended that research centers include mCRC patients in molecular screening programs in order for them to have access to innovative clinical trial agents.

As for advanced prostate cancer, ESMO does recommend that clinicians perform NGS on tissue samples to assess the tumor’s mutational status, at least for the presence of BRCA1 and BRCA2 mutations, when patients have access to the poly (ADP-ribose) polymerase inhibitors for treatment.

The authors cautioned, however, that this strategy is unlikely to be cost-effective, so larger panels should be used only when there are specific agreements with payers.

Multigene NGS is also not recommended for patients with advanced pancreatic ductal adenocarcinoma (PDAC), although ESMO points out that it is the role of research centers to propose multigene sequencing for these patients in the context of molecular screening programs.

This is again to facilitate access to innovative drugs for these patients.

Similar to recommendations for patients with advanced PDAC, patients with advanced hepatocellular carcinoma (HCC) do not need to have tumor multigene NGS either.

Considering the high unmet needs of HCC patients, ESMO feels that research centers should propose multigene sequencing to patients with advanced HCC in the context of molecular screening programs.

In contrast, ESMO recommended that tumor multigene NGS be used to detect actionable alterations in patients with advanced cholangiocarcinoma.

Again, they predict that this strategy is unlikely to be cost-effective, so larger panels should only be used if a specific agreement is in place with payers.

ESMO also assessed the frequency of level 1 alterations in less frequent tumor types, including ovarian cancers. Because BRCA1 and BRCA2 somatic mutations in ovarian tumors have been associated with increased response to the PARP inhibitors, the use of multigene NGS is justified with this malignancy, ESMO states.

The authors also recommend that tumor mutational burden be determined in cervical cancer, moderately differentiated neuroendocrine tumors, salivary cancers, vulvar cancer, and thyroid cancers.

Dr. Mosele has disclosed no relevant financial relationships. Many coauthors have relationships with the pharmaceutical industry, as listed in the article.

This article first appeared on Medscape.com.

Recommendations on the use of next-generation sequencing (NGS) tests for patients with metastatic cancer have been issued by the European Society for Medical Oncology, the first recommendations of their kind to be published by any medical society.

“Until now, there were no recommendations from scientific societies on how to use this technique in daily clinical practice to profile metastatic cancers,” Fernanda Mosele, MD, medical oncologist, Gustave Roussy, Villejuif, France, said in a statement.

NGS testing is already used extensively in oncology, particularly in metastatic cancer, she noted. The technology is used to assess the sequence of DNA in genes from a tumor tissue sample. Numerous genes can be quickly sequenced at the same time at relatively low cost. The results provide information on mutations that are present, which, in turn, helps with deciding which treatments to use, including drugs targeting the identified mutations.

“Our intent is that they [the guidelines] will unify decision-making about how NGS should be used for patients with metastatic cancer,” Dr. Mosele said.

The recommendations were published online August 25 in Annals of Oncology.

Overall, ESMO recommends the use of tumor multigene NGS for non–small cell lung cancer (NSCLC), prostate cancer, ovarian cancer, and cholangiocarcinoma.

For other cancers, the authors said that NGS is not recommended in clinical practice but could be used for research purposes.

However, patients should be informed that it is unlikely that test results would benefit them much personally.

Physicians and patients may decide together to subject the tumor to mutational testing using a large panel of genes, provided testing doesn’t burden the health care system with additional costs.

“This recommendation acknowledges that a small number of patients could benefit from a drug because they have a rare mutation,” Joaquin Mateo, MD, chair of the ESMO working group, said in a statement.

“So beyond the cancers in which everyone should receive NGS, there is room for physicians and patients to discuss the pros and cons of ordering these tests,” he added.

ESMO also does not recommend the use of off-label drugs matched to any genomic alteration detected by NGS unless an access program and a decisional procedure have been developed, either regionally or nationally.
 

No need for NGS testing of other cancers

In contrast to NSCLC, “there is currently no need to perform tumor multigene NGS for patients with mBC [metastatic breast cancer] in the context of daily practice,” ESMO stated.

This is largely because somatic sequencing cannot fully substitute for germline testing for BRCA status, and other mutations, such as HER2, can be detected using immunohistochemistry (IHC).

The same can be said for patients with metastatic gastric cancer, inasmuch as detection of alterations can and should be done using cheaper testing methods, ESMO pointed out.

However, ESMO members still emphasized that it’s important to include patients with metastatic breast cancer in molecular screening programs as well as in clinical trials testing targeted agents.

Similarly, there is no need to test metastatic colorectal cancer (mCRC) using multigene NGS in daily practice, inasmuch as most level 1 alterations in mCRC can be determined by IHC or PCR.

However, NGS can be considered as an alternative to PCR-based tests in mCRC, provided NGS is not associated with additional cost.

ESMO again recommended that research centers include mCRC patients in molecular screening programs in order for them to have access to innovative clinical trial agents.

As for advanced prostate cancer, ESMO does recommend that clinicians perform NGS on tissue samples to assess the tumor’s mutational status, at least for the presence of BRCA1 and BRCA2 mutations, when patients have access to the poly (ADP-ribose) polymerase inhibitors for treatment.

The authors cautioned, however, that this strategy is unlikely to be cost-effective, so larger panels should be used only when there are specific agreements with payers.

Multigene NGS is also not recommended for patients with advanced pancreatic ductal adenocarcinoma (PDAC), although ESMO points out that it is the role of research centers to propose multigene sequencing for these patients in the context of molecular screening programs.

This is again to facilitate access to innovative drugs for these patients.

Similar to recommendations for patients with advanced PDAC, patients with advanced hepatocellular carcinoma (HCC) do not need to have tumor multigene NGS either.

Considering the high unmet needs of HCC patients, ESMO feels that research centers should propose multigene sequencing to patients with advanced HCC in the context of molecular screening programs.

In contrast, ESMO recommended that tumor multigene NGS be used to detect actionable alterations in patients with advanced cholangiocarcinoma.

Again, they predict that this strategy is unlikely to be cost-effective, so larger panels should only be used if a specific agreement is in place with payers.

ESMO also assessed the frequency of level 1 alterations in less frequent tumor types, including ovarian cancers. Because BRCA1 and BRCA2 somatic mutations in ovarian tumors have been associated with increased response to the PARP inhibitors, the use of multigene NGS is justified with this malignancy, ESMO states.

The authors also recommend that tumor mutational burden be determined in cervical cancer, moderately differentiated neuroendocrine tumors, salivary cancers, vulvar cancer, and thyroid cancers.

Dr. Mosele has disclosed no relevant financial relationships. Many coauthors have relationships with the pharmaceutical industry, as listed in the article.

This article first appeared on Medscape.com.

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.

Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.

The study was published online August 7 in JAMA Network Open.

“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.
 

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.

No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

This article first appeared on Medscape.com .

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.

Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.

The study was published online August 7 in JAMA Network Open.

“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.
 

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.

No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

This article first appeared on Medscape.com .

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.

Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.

The study was published online August 7 in JAMA Network Open.

“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.
 

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.

No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

This article first appeared on Medscape.com .

Clinical data for the first-ever RET inhibitor, selpercatinib (Retevmo), show efficacy in two groups of patients with cancer – those with RET fusion–positive non–small cell lung cancer (NSCLC), and those with RET-mutant medullary thyroid cancer (MTC).

The drug showed “very good efficacy and also very good tolerability” in both groups, said lead author Lori J. Wirth, MD, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center, Boston, in a statement.

“The response rates are high, responses are very durable, and overall, the drug does not cause a lot of toxicity,” she said.

“If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile,” Dr. Wirth added.

Both groups of patients were part of the phase 1/2 LIBRETTO-001 study, which served as the basis for the recent accelerated approval of selpercatinib by the Food and Drug Administration.

Data from LIBRETTO-001 were published in the New England Journal of Medicine as two articles, one on NSCLC patients and one on MTC patients.

There has been a “remarkable increase” in the number of targeted agents that are effective in treating patients with advanced cancers that harbor specific genomic alterations, commented Razelle Kurzrock, MD, from the University of California, San Diego, in an accompanying editorial.

Selpercatinib, a potent RET inhibitor, “is now poised to alter the landscape of another genomic subgroup – RET-altered cancers,” she wrote.

Multikinase inhibitors such as vandetanib and cabozantinib have ancillary RET-inhibitor activity and are also active against RET-driven cancers. But these drugs are limited by off-target side effects, Dr. Krurzrock pointed out. “In contrast, next-generation, highly potent, and selective RET inhibitors such as selpercatinib offer the potential for improved efficacy and a more satisfactory side effect profile.”

In both parts of the study, selpercatinib produced durable responses in a majority of patients. Only about 3% of patients discontinued taking selpercatinib because of drug-related adverse events.

Taken together, these results show that selpercatinib “had marked and durable antitumor activity in most patients with RET-altered thyroid cancer or NSCLC,” wrote Dr. Krurzrock. “RET abnormalities now join other genomic alterations such as NTRK fusions, tumor mutational burden, and deficient mismatchrepair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies.”

Results in patients with RET-mutated NSCLC

All patients enrolled in the LIBRETTO-001 trial received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

Of 105 patients with NSCLC who had received at least one platinum-based chemotherapy regimen, the objective response rate was 64%. The median duration of response was 17.5 months.

At a median follow-up of 12.1 months, 63% of the responses were ongoing.

The cohort included 39 treatment-naive patients, among whom the response rate was even higher, at 85%; 90% of the responses were ongoing at 6 months. In addition, 11 patients had measurable central nervous system metastasis at study enrollment. Of this group, 91% achieved an intracranial response.

Common adverse events of grade 3 or higher included hypertension (in 14% of the patients), an increase in ALT level (in 12%), an increase in AST level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). The drug was discontinued in 12 patients because of a drug-related adverse event.
 

Results in patients with RET-mutated MTC

Efficacy for MTC was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The objective response rate was 69%. The 1-year progression-free survival rate was 82%.

For the 88 patients who had not previously received vandetanib or cabozantinib, the response rate was 73%. The 1-year progression-free survival rate was 92%.

In a subgroup of 19 patients with previously treated RET fusion–positive thyroid cancer, 79% responded to the therapy; 1-year progression-free survival was 64%.

The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), an increase in ALT level (in 11%), an increase in AST level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Selpercatinib was discontinued by 12 patients because of drug-related adverse events.

The study was funded by Loxo Oncology (a wholly owned subsidiary of Eli Lilly) and by grants from the National Institutes of Health and the University of Texas MD Anderson Cancer Center. Kurzrock and Wirth report relationships with numerous pharmaceutical companies, as listed in the journal article.

This article first appeared on Medscape.com.

Clinical data for the first-ever RET inhibitor, selpercatinib (Retevmo), show efficacy in two groups of patients with cancer – those with RET fusion–positive non–small cell lung cancer (NSCLC), and those with RET-mutant medullary thyroid cancer (MTC).

The drug showed “very good efficacy and also very good tolerability” in both groups, said lead author Lori J. Wirth, MD, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center, Boston, in a statement.

“The response rates are high, responses are very durable, and overall, the drug does not cause a lot of toxicity,” she said.

“If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile,” Dr. Wirth added.

Both groups of patients were part of the phase 1/2 LIBRETTO-001 study, which served as the basis for the recent accelerated approval of selpercatinib by the Food and Drug Administration.

Data from LIBRETTO-001 were published in the New England Journal of Medicine as two articles, one on NSCLC patients and one on MTC patients.

There has been a “remarkable increase” in the number of targeted agents that are effective in treating patients with advanced cancers that harbor specific genomic alterations, commented Razelle Kurzrock, MD, from the University of California, San Diego, in an accompanying editorial.

Selpercatinib, a potent RET inhibitor, “is now poised to alter the landscape of another genomic subgroup – RET-altered cancers,” she wrote.

Multikinase inhibitors such as vandetanib and cabozantinib have ancillary RET-inhibitor activity and are also active against RET-driven cancers. But these drugs are limited by off-target side effects, Dr. Krurzrock pointed out. “In contrast, next-generation, highly potent, and selective RET inhibitors such as selpercatinib offer the potential for improved efficacy and a more satisfactory side effect profile.”

In both parts of the study, selpercatinib produced durable responses in a majority of patients. Only about 3% of patients discontinued taking selpercatinib because of drug-related adverse events.

Taken together, these results show that selpercatinib “had marked and durable antitumor activity in most patients with RET-altered thyroid cancer or NSCLC,” wrote Dr. Krurzrock. “RET abnormalities now join other genomic alterations such as NTRK fusions, tumor mutational burden, and deficient mismatchrepair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies.”

Results in patients with RET-mutated NSCLC

All patients enrolled in the LIBRETTO-001 trial received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

Of 105 patients with NSCLC who had received at least one platinum-based chemotherapy regimen, the objective response rate was 64%. The median duration of response was 17.5 months.

At a median follow-up of 12.1 months, 63% of the responses were ongoing.

The cohort included 39 treatment-naive patients, among whom the response rate was even higher, at 85%; 90% of the responses were ongoing at 6 months. In addition, 11 patients had measurable central nervous system metastasis at study enrollment. Of this group, 91% achieved an intracranial response.

Common adverse events of grade 3 or higher included hypertension (in 14% of the patients), an increase in ALT level (in 12%), an increase in AST level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). The drug was discontinued in 12 patients because of a drug-related adverse event.
 

Results in patients with RET-mutated MTC

Efficacy for MTC was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The objective response rate was 69%. The 1-year progression-free survival rate was 82%.

For the 88 patients who had not previously received vandetanib or cabozantinib, the response rate was 73%. The 1-year progression-free survival rate was 92%.

In a subgroup of 19 patients with previously treated RET fusion–positive thyroid cancer, 79% responded to the therapy; 1-year progression-free survival was 64%.

The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), an increase in ALT level (in 11%), an increase in AST level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Selpercatinib was discontinued by 12 patients because of drug-related adverse events.

The study was funded by Loxo Oncology (a wholly owned subsidiary of Eli Lilly) and by grants from the National Institutes of Health and the University of Texas MD Anderson Cancer Center. Kurzrock and Wirth report relationships with numerous pharmaceutical companies, as listed in the journal article.

This article first appeared on Medscape.com.

Clinical data for the first-ever RET inhibitor, selpercatinib (Retevmo), show efficacy in two groups of patients with cancer – those with RET fusion–positive non–small cell lung cancer (NSCLC), and those with RET-mutant medullary thyroid cancer (MTC).

The drug showed “very good efficacy and also very good tolerability” in both groups, said lead author Lori J. Wirth, MD, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center, Boston, in a statement.

“The response rates are high, responses are very durable, and overall, the drug does not cause a lot of toxicity,” she said.

“If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile,” Dr. Wirth added.

Both groups of patients were part of the phase 1/2 LIBRETTO-001 study, which served as the basis for the recent accelerated approval of selpercatinib by the Food and Drug Administration.

Data from LIBRETTO-001 were published in the New England Journal of Medicine as two articles, one on NSCLC patients and one on MTC patients.

There has been a “remarkable increase” in the number of targeted agents that are effective in treating patients with advanced cancers that harbor specific genomic alterations, commented Razelle Kurzrock, MD, from the University of California, San Diego, in an accompanying editorial.

Selpercatinib, a potent RET inhibitor, “is now poised to alter the landscape of another genomic subgroup – RET-altered cancers,” she wrote.

Multikinase inhibitors such as vandetanib and cabozantinib have ancillary RET-inhibitor activity and are also active against RET-driven cancers. But these drugs are limited by off-target side effects, Dr. Krurzrock pointed out. “In contrast, next-generation, highly potent, and selective RET inhibitors such as selpercatinib offer the potential for improved efficacy and a more satisfactory side effect profile.”

In both parts of the study, selpercatinib produced durable responses in a majority of patients. Only about 3% of patients discontinued taking selpercatinib because of drug-related adverse events.

Taken together, these results show that selpercatinib “had marked and durable antitumor activity in most patients with RET-altered thyroid cancer or NSCLC,” wrote Dr. Krurzrock. “RET abnormalities now join other genomic alterations such as NTRK fusions, tumor mutational burden, and deficient mismatchrepair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies.”

Results in patients with RET-mutated NSCLC

All patients enrolled in the LIBRETTO-001 trial received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

Of 105 patients with NSCLC who had received at least one platinum-based chemotherapy regimen, the objective response rate was 64%. The median duration of response was 17.5 months.

At a median follow-up of 12.1 months, 63% of the responses were ongoing.

The cohort included 39 treatment-naive patients, among whom the response rate was even higher, at 85%; 90% of the responses were ongoing at 6 months. In addition, 11 patients had measurable central nervous system metastasis at study enrollment. Of this group, 91% achieved an intracranial response.

Common adverse events of grade 3 or higher included hypertension (in 14% of the patients), an increase in ALT level (in 12%), an increase in AST level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). The drug was discontinued in 12 patients because of a drug-related adverse event.
 

Results in patients with RET-mutated MTC

Efficacy for MTC was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The objective response rate was 69%. The 1-year progression-free survival rate was 82%.

For the 88 patients who had not previously received vandetanib or cabozantinib, the response rate was 73%. The 1-year progression-free survival rate was 92%.

In a subgroup of 19 patients with previously treated RET fusion–positive thyroid cancer, 79% responded to the therapy; 1-year progression-free survival was 64%.

The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), an increase in ALT level (in 11%), an increase in AST level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Selpercatinib was discontinued by 12 patients because of drug-related adverse events.

The study was funded by Loxo Oncology (a wholly owned subsidiary of Eli Lilly) and by grants from the National Institutes of Health and the University of Texas MD Anderson Cancer Center. Kurzrock and Wirth report relationships with numerous pharmaceutical companies, as listed in the journal article.

This article first appeared on Medscape.com.