Lung Cancer

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

A combination of capmatinib and gefitinib shows promise for patients with EGFR-mutated, MET-dysregulated non–small-cell lung cancer (NSCLC) after EGFR inhibitor failure, investigators said.

Patients with MET-amplified disease had the most robust responses, reported lead author Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute in Guangzhou, China, and his colleagues.

“Patients with EGFR-mutated NSCLC usually relapse within a year, despite high response rates to EGFR-TKIs,” the authors wrote in the Journal of Clinical Oncology. MET amplification is responsible for resistance in 5%-26% of NSCLC cases with EGFR inhibitor resistance.

Capmatinib is a highly specific MET inhibitor that has been effective in preclinical models as a single agent and in combination with first- or third-generation EGFR-TKIs. It also promotes apoptosis and restores erlotinib sensitivity in erlotinib-resistant NSCLC. Gefitinib, like erlotinib, is an EGFR-TKI.

The phase 1b/2 study involved 161 patients with EGFR-mutated, MET-dysregulated (amplified/overexpressed) NSCLC who had disease progression during EGFR-TKI therapy. In the dose escalating, phase 1b portion of the study, 61 patients received capmatinib 100-800 mg daily or 200-600 mg twice daily, plus gefitinib 250 mg daily. During phase 2, 100 patients received capmatinib 400 mg twice daily plus gefitinib 250 mg daily. The primary endpoint was overall response rate (ORR).

Across both phases of the study, approximately one-quarter of the patients responded to the drug combination (ORR = 27%). In patients with a high level of MET amplification (MET gene copy number greater than or equal to 6), responses were more common, with almost half of the patients responding (ORR = 47%).

The treatment regimen was generally well tolerated. The most common adverse events were nausea (28%), peripheral edema (22%), reduced appetite (21%), and rash (20%). Grade 3 or higher adverse events were uncommon; increased lipase and increased amylase occurred most frequently (6% for each).

“The combination of capmatinib with gefitinib has been shown to be both feasible and rational,” the authors concluded, “and the data from this study suggest that the combination of capmatinib with an EGFR-TKI may be a promising treatment option for patients with EGFR-mutated, MET-dysregulated NSCLC and particularly for patients with MET-amplified tumors.”

Novartis funded the study. The authors reported affiliations with Novartis and others.

SOURCE: Wu et al. J Clin Oncol. Aug 29. doi: 10.1200/JCO.2018.77.7326.

A combination of capmatinib and gefitinib shows promise for patients with EGFR-mutated, MET-dysregulated non–small-cell lung cancer (NSCLC) after EGFR inhibitor failure, investigators said.

Patients with MET-amplified disease had the most robust responses, reported lead author Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute in Guangzhou, China, and his colleagues.

“Patients with EGFR-mutated NSCLC usually relapse within a year, despite high response rates to EGFR-TKIs,” the authors wrote in the Journal of Clinical Oncology. MET amplification is responsible for resistance in 5%-26% of NSCLC cases with EGFR inhibitor resistance.

Capmatinib is a highly specific MET inhibitor that has been effective in preclinical models as a single agent and in combination with first- or third-generation EGFR-TKIs. It also promotes apoptosis and restores erlotinib sensitivity in erlotinib-resistant NSCLC. Gefitinib, like erlotinib, is an EGFR-TKI.

The phase 1b/2 study involved 161 patients with EGFR-mutated, MET-dysregulated (amplified/overexpressed) NSCLC who had disease progression during EGFR-TKI therapy. In the dose escalating, phase 1b portion of the study, 61 patients received capmatinib 100-800 mg daily or 200-600 mg twice daily, plus gefitinib 250 mg daily. During phase 2, 100 patients received capmatinib 400 mg twice daily plus gefitinib 250 mg daily. The primary endpoint was overall response rate (ORR).

Across both phases of the study, approximately one-quarter of the patients responded to the drug combination (ORR = 27%). In patients with a high level of MET amplification (MET gene copy number greater than or equal to 6), responses were more common, with almost half of the patients responding (ORR = 47%).

The treatment regimen was generally well tolerated. The most common adverse events were nausea (28%), peripheral edema (22%), reduced appetite (21%), and rash (20%). Grade 3 or higher adverse events were uncommon; increased lipase and increased amylase occurred most frequently (6% for each).

“The combination of capmatinib with gefitinib has been shown to be both feasible and rational,” the authors concluded, “and the data from this study suggest that the combination of capmatinib with an EGFR-TKI may be a promising treatment option for patients with EGFR-mutated, MET-dysregulated NSCLC and particularly for patients with MET-amplified tumors.”

Novartis funded the study. The authors reported affiliations with Novartis and others.

SOURCE: Wu et al. J Clin Oncol. Aug 29. doi: 10.1200/JCO.2018.77.7326.

A combination of capmatinib and gefitinib shows promise for patients with EGFR-mutated, MET-dysregulated non–small-cell lung cancer (NSCLC) after EGFR inhibitor failure, investigators said.

Patients with MET-amplified disease had the most robust responses, reported lead author Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute in Guangzhou, China, and his colleagues.

“Patients with EGFR-mutated NSCLC usually relapse within a year, despite high response rates to EGFR-TKIs,” the authors wrote in the Journal of Clinical Oncology. MET amplification is responsible for resistance in 5%-26% of NSCLC cases with EGFR inhibitor resistance.

Capmatinib is a highly specific MET inhibitor that has been effective in preclinical models as a single agent and in combination with first- or third-generation EGFR-TKIs. It also promotes apoptosis and restores erlotinib sensitivity in erlotinib-resistant NSCLC. Gefitinib, like erlotinib, is an EGFR-TKI.

The phase 1b/2 study involved 161 patients with EGFR-mutated, MET-dysregulated (amplified/overexpressed) NSCLC who had disease progression during EGFR-TKI therapy. In the dose escalating, phase 1b portion of the study, 61 patients received capmatinib 100-800 mg daily or 200-600 mg twice daily, plus gefitinib 250 mg daily. During phase 2, 100 patients received capmatinib 400 mg twice daily plus gefitinib 250 mg daily. The primary endpoint was overall response rate (ORR).

Across both phases of the study, approximately one-quarter of the patients responded to the drug combination (ORR = 27%). In patients with a high level of MET amplification (MET gene copy number greater than or equal to 6), responses were more common, with almost half of the patients responding (ORR = 47%).

The treatment regimen was generally well tolerated. The most common adverse events were nausea (28%), peripheral edema (22%), reduced appetite (21%), and rash (20%). Grade 3 or higher adverse events were uncommon; increased lipase and increased amylase occurred most frequently (6% for each).

“The combination of capmatinib with gefitinib has been shown to be both feasible and rational,” the authors concluded, “and the data from this study suggest that the combination of capmatinib with an EGFR-TKI may be a promising treatment option for patients with EGFR-mutated, MET-dysregulated NSCLC and particularly for patients with MET-amplified tumors.”

Novartis funded the study. The authors reported affiliations with Novartis and others.

SOURCE: Wu et al. J Clin Oncol. Aug 29. doi: 10.1200/JCO.2018.77.7326.

Among scenarios where immune checkpoint inhibitors (ICIs) might be combined, particular caution is needed in the setting of brain metastases, according to authors of a recent clinical review.

While evidence to date is mixed, some studies do suggest that adding ICIs to high-dose stereotactic intracranial radiotherapy for brain metastases might increase the risk of treatment-related brain necrosis, the authors said.

By contrast, the balance of evidence suggests ICIs can be safely combined with palliative radiotherapy without site-specific increases in adverse events, they added.

Likewise, in patients with non–small-cell lung cancer, ICIs do not appear to increase incidence of grade 3 or greater pneumonitis when given after definitive chemoradiotherapy, in both retrospective and prospective investigations.

Nevertheless, the addition of ICIs to radiotherapy requires careful further study because of the potential for increased type or severity of toxicities, including the immune-related adverse events associated with ICIs, wrote corresponding author Jay S. Loeffler, MD, of Massachusetts General Hospital, Boston, and his colleagues.

“Caution is warranted when combining radiotherapy and ICI, especially with intracranial radiotherapy,” the researchers wrote. Their report is in Nature Reviews Clinical Oncology.

Some studies have indicated a higher rate of treatment-associated brain necrosis when ICIs are combined with intracranial radiotherapy, while others have shown no such trend, the authors said.

In one single-institution experience involving 180 patients with brain metastases undergoing stereotactic radiotherapy, incidence of treatment-associated brain necrosis was significantly higher in patients receiving an ICI, with an odds ratio of 2.4 (95% confidence interval, 1.06-5.44; P = .03).

Similarly, a retrospective single institution 480-patient study showed an incidence of treatment-associated brain necrosis of 20% for ICIs plus stereotactic radiotherapy versus 7% for radiotherapy alone (P less than .001), but substantial differences in baseline characteristics between groups limited the strength of the study’s conclusions, according to the researchers.

Increased risk is primarily in the form of asymptomatic or minimally symptomatic episodes in some series, the authors noted. A retrospective, 54-patient report showed a rate of treatment-associated brain necrosis of 30% when ICIs were combined with stereotactic radiotherapy, versus 21% for radiotherapy alone (P = .08), but the incidence of symptomatic cases was 15% in both groups, they noted.

“Intriguingly, the findings of several studies have demonstrated an association between [treatment-associated brain necrosis] and improved survival outcomes in patients with melanoma brain metastases that is similar to the independent observations of an analogous relationship between risk of [immune-related adverse events] in general and responsiveness to ICI,” the researchers wrote.

Most of the Food and Drug Administration–approved indications for ICIs are in the metastatic setting, where palliative radiotherapy is frequently important, the authors noted.

In two retrospective studies of patients with metastatic cancers receiving palliative radiotherapy with ICIs, there was a lack of clear association between the irradiated site and specific immune-related adverse events; that lack of association suggests that any toxicities arising from interactions between palliative radiotherapy and ICIs are mainly systemic, rather than local, the authors wrote.

Several retrospective series in advanced-stage melanoma patients have suggested that palliative radiotherapy plus ICIs is safe and does not significantly increase incidence of immune-related adverse events. However, findings from one series showed a correlation between both the ICI and radiotherapy dose given and the incidence of immune-related adverse events.

Prospective studies will be essential to optimize the balance between disease control and risk of morbidity associated with ICIs and radiotherapy combinations, the authors concluded.

The researchers declared no competing interests related to their review article.

SOURCE: Hwang WL, et al. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494.

Among scenarios where immune checkpoint inhibitors (ICIs) might be combined, particular caution is needed in the setting of brain metastases, according to authors of a recent clinical review.

While evidence to date is mixed, some studies do suggest that adding ICIs to high-dose stereotactic intracranial radiotherapy for brain metastases might increase the risk of treatment-related brain necrosis, the authors said.

By contrast, the balance of evidence suggests ICIs can be safely combined with palliative radiotherapy without site-specific increases in adverse events, they added.

Likewise, in patients with non–small-cell lung cancer, ICIs do not appear to increase incidence of grade 3 or greater pneumonitis when given after definitive chemoradiotherapy, in both retrospective and prospective investigations.

Nevertheless, the addition of ICIs to radiotherapy requires careful further study because of the potential for increased type or severity of toxicities, including the immune-related adverse events associated with ICIs, wrote corresponding author Jay S. Loeffler, MD, of Massachusetts General Hospital, Boston, and his colleagues.

“Caution is warranted when combining radiotherapy and ICI, especially with intracranial radiotherapy,” the researchers wrote. Their report is in Nature Reviews Clinical Oncology.

Some studies have indicated a higher rate of treatment-associated brain necrosis when ICIs are combined with intracranial radiotherapy, while others have shown no such trend, the authors said.

In one single-institution experience involving 180 patients with brain metastases undergoing stereotactic radiotherapy, incidence of treatment-associated brain necrosis was significantly higher in patients receiving an ICI, with an odds ratio of 2.4 (95% confidence interval, 1.06-5.44; P = .03).

Similarly, a retrospective single institution 480-patient study showed an incidence of treatment-associated brain necrosis of 20% for ICIs plus stereotactic radiotherapy versus 7% for radiotherapy alone (P less than .001), but substantial differences in baseline characteristics between groups limited the strength of the study’s conclusions, according to the researchers.

Increased risk is primarily in the form of asymptomatic or minimally symptomatic episodes in some series, the authors noted. A retrospective, 54-patient report showed a rate of treatment-associated brain necrosis of 30% when ICIs were combined with stereotactic radiotherapy, versus 21% for radiotherapy alone (P = .08), but the incidence of symptomatic cases was 15% in both groups, they noted.

“Intriguingly, the findings of several studies have demonstrated an association between [treatment-associated brain necrosis] and improved survival outcomes in patients with melanoma brain metastases that is similar to the independent observations of an analogous relationship between risk of [immune-related adverse events] in general and responsiveness to ICI,” the researchers wrote.

Most of the Food and Drug Administration–approved indications for ICIs are in the metastatic setting, where palliative radiotherapy is frequently important, the authors noted.

In two retrospective studies of patients with metastatic cancers receiving palliative radiotherapy with ICIs, there was a lack of clear association between the irradiated site and specific immune-related adverse events; that lack of association suggests that any toxicities arising from interactions between palliative radiotherapy and ICIs are mainly systemic, rather than local, the authors wrote.

Several retrospective series in advanced-stage melanoma patients have suggested that palliative radiotherapy plus ICIs is safe and does not significantly increase incidence of immune-related adverse events. However, findings from one series showed a correlation between both the ICI and radiotherapy dose given and the incidence of immune-related adverse events.

Prospective studies will be essential to optimize the balance between disease control and risk of morbidity associated with ICIs and radiotherapy combinations, the authors concluded.

The researchers declared no competing interests related to their review article.

SOURCE: Hwang WL, et al. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494.

Among scenarios where immune checkpoint inhibitors (ICIs) might be combined, particular caution is needed in the setting of brain metastases, according to authors of a recent clinical review.

While evidence to date is mixed, some studies do suggest that adding ICIs to high-dose stereotactic intracranial radiotherapy for brain metastases might increase the risk of treatment-related brain necrosis, the authors said.

By contrast, the balance of evidence suggests ICIs can be safely combined with palliative radiotherapy without site-specific increases in adverse events, they added.

Likewise, in patients with non–small-cell lung cancer, ICIs do not appear to increase incidence of grade 3 or greater pneumonitis when given after definitive chemoradiotherapy, in both retrospective and prospective investigations.

Nevertheless, the addition of ICIs to radiotherapy requires careful further study because of the potential for increased type or severity of toxicities, including the immune-related adverse events associated with ICIs, wrote corresponding author Jay S. Loeffler, MD, of Massachusetts General Hospital, Boston, and his colleagues.

“Caution is warranted when combining radiotherapy and ICI, especially with intracranial radiotherapy,” the researchers wrote. Their report is in Nature Reviews Clinical Oncology.

Some studies have indicated a higher rate of treatment-associated brain necrosis when ICIs are combined with intracranial radiotherapy, while others have shown no such trend, the authors said.

In one single-institution experience involving 180 patients with brain metastases undergoing stereotactic radiotherapy, incidence of treatment-associated brain necrosis was significantly higher in patients receiving an ICI, with an odds ratio of 2.4 (95% confidence interval, 1.06-5.44; P = .03).

Similarly, a retrospective single institution 480-patient study showed an incidence of treatment-associated brain necrosis of 20% for ICIs plus stereotactic radiotherapy versus 7% for radiotherapy alone (P less than .001), but substantial differences in baseline characteristics between groups limited the strength of the study’s conclusions, according to the researchers.

Increased risk is primarily in the form of asymptomatic or minimally symptomatic episodes in some series, the authors noted. A retrospective, 54-patient report showed a rate of treatment-associated brain necrosis of 30% when ICIs were combined with stereotactic radiotherapy, versus 21% for radiotherapy alone (P = .08), but the incidence of symptomatic cases was 15% in both groups, they noted.

“Intriguingly, the findings of several studies have demonstrated an association between [treatment-associated brain necrosis] and improved survival outcomes in patients with melanoma brain metastases that is similar to the independent observations of an analogous relationship between risk of [immune-related adverse events] in general and responsiveness to ICI,” the researchers wrote.

Most of the Food and Drug Administration–approved indications for ICIs are in the metastatic setting, where palliative radiotherapy is frequently important, the authors noted.

In two retrospective studies of patients with metastatic cancers receiving palliative radiotherapy with ICIs, there was a lack of clear association between the irradiated site and specific immune-related adverse events; that lack of association suggests that any toxicities arising from interactions between palliative radiotherapy and ICIs are mainly systemic, rather than local, the authors wrote.

Several retrospective series in advanced-stage melanoma patients have suggested that palliative radiotherapy plus ICIs is safe and does not significantly increase incidence of immune-related adverse events. However, findings from one series showed a correlation between both the ICI and radiotherapy dose given and the incidence of immune-related adverse events.

Prospective studies will be essential to optimize the balance between disease control and risk of morbidity associated with ICIs and radiotherapy combinations, the authors concluded.

The researchers declared no competing interests related to their review article.

SOURCE: Hwang WL, et al. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494.

More frequent imaging didn’t improve 5-year survival in patients with resected non–small cell lung carcinoma, even after researchers controlled for tumor histology and recurrence.

windcatcher/Thinkstock.com

Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.

The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.

“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”

However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”

The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.

“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”

The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.

The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.

After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).

Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).

Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.

“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.

The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.

The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.

“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”

However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”

The authors reported no financial conflicts.

msullivan@mdedge.com

SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.

More frequent imaging didn’t improve 5-year survival in patients with resected non–small cell lung carcinoma, even after researchers controlled for tumor histology and recurrence.

windcatcher/Thinkstock.com

Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.

The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.

“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”

However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”

The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.

“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”

The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.

The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.

After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).

Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).

Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.

“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.

The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.

The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.

“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”

However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”

The authors reported no financial conflicts.

msullivan@mdedge.com

SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.

More frequent imaging didn’t improve 5-year survival in patients with resected non–small cell lung carcinoma, even after researchers controlled for tumor histology and recurrence.

windcatcher/Thinkstock.com

Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.

The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.

“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”

However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”

The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.

“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”

The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.

The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.

After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).

Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).

Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.

“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.

The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.

The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.

“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”

However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”

The authors reported no financial conflicts.

msullivan@mdedge.com

SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.

Immune checkpoint inhibitor therapy may be less effective if the patient is receiving corticosteroids at the time that treatment is initiated, results of a retrospective, two-center analysis suggest.

Corticosteroid use at the time of starting a PD-1 or PD-L1 inhibitor was associated with significantly reduced overall survival and progression-free survival in patients with non–small-cell lung cancer, the authors of the analysis reported.

“Prudent use of corticosteroids at the time of initiating PD-1/PD-L1 blockade is warranted,” said Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors. The report is in the Journal of Clinical Oncology.

The retrospective analysis from Dr. Hellmann and his colleagues comprised 640 patients treated with single-agent atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center, Villejuif, France, between April 2011 and September 2017.

Ninety of those patients (14%) were receiving at least 10 mg of prednisone equivalent at the time the immune checkpoint inhibitor was started, a review of patient records revealed. About one-third were receiving corticosteroids for dyspnea or other respiratory symptoms. Another 21% had fatigue and 19% had brain metastases prompting corticosteroid treatment.

Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001), as well as decreased overall response rate in a multivariable analysis adjusted for performance status, history of smoking, and history of brain metastases, the investigators reported.

Reduced efficacy also was seen in analyses that looked at each center separately. For the Memorial Sloan Kettering cohort (455 patients), baseline corticosteroid use was associated with significantly decreased overall response rate, shorter progression-free survival, and shorter overall survival.

For the smaller French cohort, (185 patients), there was a statistically nonsignificant decrease in overall response rate, along with significant reductions in progression-free survival and overall survival.

Based on these data, it may be prudent to try other pharmacologic or nonpharmacologic strategies to manage cancer symptoms if treatment with a PD-1/PD-L1 blocker is planned, Dr. Hellmann and his coauthors said.

“These strategies could enable patients to be tapered off corticosteroids before the start of PD-1/PD-L1 blockade to potentially achieve maximum benefit from these agents,” they wrote.

However, medically necessary corticosteroids should not be avoided, such as those given for management of brain metastases, they added.

Interestingly, other recent studies have suggested that patients already on PD-1/PD-L1 inhibitors do not seem to have decreased efficacy when corticosteroids are prescribed to manage emergent immune-related adverse events.

That’s “fortunate,” given that corticosteroids are a mainstay for the management of these characteristic adverse events in patients receiving immune checkpoint inhibitors, they said.

Dr. Hellmann reported research funding from Bristol-Myers Squibb, and a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Shattuck Labs, and Syndax. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Pfizer, and Roche, among others.

SOURCE: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.

Immune checkpoint inhibitor therapy may be less effective if the patient is receiving corticosteroids at the time that treatment is initiated, results of a retrospective, two-center analysis suggest.

Corticosteroid use at the time of starting a PD-1 or PD-L1 inhibitor was associated with significantly reduced overall survival and progression-free survival in patients with non–small-cell lung cancer, the authors of the analysis reported.

“Prudent use of corticosteroids at the time of initiating PD-1/PD-L1 blockade is warranted,” said Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors. The report is in the Journal of Clinical Oncology.

The retrospective analysis from Dr. Hellmann and his colleagues comprised 640 patients treated with single-agent atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center, Villejuif, France, between April 2011 and September 2017.

Ninety of those patients (14%) were receiving at least 10 mg of prednisone equivalent at the time the immune checkpoint inhibitor was started, a review of patient records revealed. About one-third were receiving corticosteroids for dyspnea or other respiratory symptoms. Another 21% had fatigue and 19% had brain metastases prompting corticosteroid treatment.

Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001), as well as decreased overall response rate in a multivariable analysis adjusted for performance status, history of smoking, and history of brain metastases, the investigators reported.

Reduced efficacy also was seen in analyses that looked at each center separately. For the Memorial Sloan Kettering cohort (455 patients), baseline corticosteroid use was associated with significantly decreased overall response rate, shorter progression-free survival, and shorter overall survival.

For the smaller French cohort, (185 patients), there was a statistically nonsignificant decrease in overall response rate, along with significant reductions in progression-free survival and overall survival.

Based on these data, it may be prudent to try other pharmacologic or nonpharmacologic strategies to manage cancer symptoms if treatment with a PD-1/PD-L1 blocker is planned, Dr. Hellmann and his coauthors said.

“These strategies could enable patients to be tapered off corticosteroids before the start of PD-1/PD-L1 blockade to potentially achieve maximum benefit from these agents,” they wrote.

However, medically necessary corticosteroids should not be avoided, such as those given for management of brain metastases, they added.

Interestingly, other recent studies have suggested that patients already on PD-1/PD-L1 inhibitors do not seem to have decreased efficacy when corticosteroids are prescribed to manage emergent immune-related adverse events.

That’s “fortunate,” given that corticosteroids are a mainstay for the management of these characteristic adverse events in patients receiving immune checkpoint inhibitors, they said.

Dr. Hellmann reported research funding from Bristol-Myers Squibb, and a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Shattuck Labs, and Syndax. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Pfizer, and Roche, among others.

SOURCE: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.

Immune checkpoint inhibitor therapy may be less effective if the patient is receiving corticosteroids at the time that treatment is initiated, results of a retrospective, two-center analysis suggest.

Corticosteroid use at the time of starting a PD-1 or PD-L1 inhibitor was associated with significantly reduced overall survival and progression-free survival in patients with non–small-cell lung cancer, the authors of the analysis reported.

“Prudent use of corticosteroids at the time of initiating PD-1/PD-L1 blockade is warranted,” said Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors. The report is in the Journal of Clinical Oncology.

The retrospective analysis from Dr. Hellmann and his colleagues comprised 640 patients treated with single-agent atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center, Villejuif, France, between April 2011 and September 2017.

Ninety of those patients (14%) were receiving at least 10 mg of prednisone equivalent at the time the immune checkpoint inhibitor was started, a review of patient records revealed. About one-third were receiving corticosteroids for dyspnea or other respiratory symptoms. Another 21% had fatigue and 19% had brain metastases prompting corticosteroid treatment.

Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001), as well as decreased overall response rate in a multivariable analysis adjusted for performance status, history of smoking, and history of brain metastases, the investigators reported.

Reduced efficacy also was seen in analyses that looked at each center separately. For the Memorial Sloan Kettering cohort (455 patients), baseline corticosteroid use was associated with significantly decreased overall response rate, shorter progression-free survival, and shorter overall survival.

For the smaller French cohort, (185 patients), there was a statistically nonsignificant decrease in overall response rate, along with significant reductions in progression-free survival and overall survival.

Based on these data, it may be prudent to try other pharmacologic or nonpharmacologic strategies to manage cancer symptoms if treatment with a PD-1/PD-L1 blocker is planned, Dr. Hellmann and his coauthors said.

“These strategies could enable patients to be tapered off corticosteroids before the start of PD-1/PD-L1 blockade to potentially achieve maximum benefit from these agents,” they wrote.

However, medically necessary corticosteroids should not be avoided, such as those given for management of brain metastases, they added.

Interestingly, other recent studies have suggested that patients already on PD-1/PD-L1 inhibitors do not seem to have decreased efficacy when corticosteroids are prescribed to manage emergent immune-related adverse events.

That’s “fortunate,” given that corticosteroids are a mainstay for the management of these characteristic adverse events in patients receiving immune checkpoint inhibitors, they said.

Dr. Hellmann reported research funding from Bristol-Myers Squibb, and a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Shattuck Labs, and Syndax. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Pfizer, and Roche, among others.

SOURCE: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.

The Food and Drug Administration has now granted full approval to pembrolizumab (Keytruda) in combination with pemetrexed (Alimta) and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

The checkpoint inhibitor was previously approved for patients with metastatic nonsquamous NSCLC in 2017, under the accelerated approval process, based on phase 2 results. Approval is now converted to a full approval, based on the results of the phase 3 Keynote-189 trial.

Patients in Keynote-189 who received pembrolizumab in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (hazard ratio, 0.49 [95% confidence interval, 0.38-0.64]; P less than .00001), according to the company press statement.

There was also a significant improvement in progression-free survival (PFS) with the pembrolizumab plus chemotherapy combination, compared with chemotherapy alone (HR, 0.52 [95% CI, 0.43-0.64]; P less than .00001).

Patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for four cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or cisplatin or carboplatin and pemetrexed intravenously every 3 weeks for four cycles followed by pemetrexed every 3 weeks (n = 206). Treatment continued until progression of disease or unacceptable toxicity.

The most common adverse reactions with pembrolizumab, resulting in discontinuation, were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions or laboratory abnormalities resulting in interruption of treatment were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%).

The Food and Drug Administration has now granted full approval to pembrolizumab (Keytruda) in combination with pemetrexed (Alimta) and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

The checkpoint inhibitor was previously approved for patients with metastatic nonsquamous NSCLC in 2017, under the accelerated approval process, based on phase 2 results. Approval is now converted to a full approval, based on the results of the phase 3 Keynote-189 trial.

Patients in Keynote-189 who received pembrolizumab in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (hazard ratio, 0.49 [95% confidence interval, 0.38-0.64]; P less than .00001), according to the company press statement.

There was also a significant improvement in progression-free survival (PFS) with the pembrolizumab plus chemotherapy combination, compared with chemotherapy alone (HR, 0.52 [95% CI, 0.43-0.64]; P less than .00001).

Patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for four cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or cisplatin or carboplatin and pemetrexed intravenously every 3 weeks for four cycles followed by pemetrexed every 3 weeks (n = 206). Treatment continued until progression of disease or unacceptable toxicity.

The most common adverse reactions with pembrolizumab, resulting in discontinuation, were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions or laboratory abnormalities resulting in interruption of treatment were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%).

The Food and Drug Administration has now granted full approval to pembrolizumab (Keytruda) in combination with pemetrexed (Alimta) and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

The checkpoint inhibitor was previously approved for patients with metastatic nonsquamous NSCLC in 2017, under the accelerated approval process, based on phase 2 results. Approval is now converted to a full approval, based on the results of the phase 3 Keynote-189 trial.

Patients in Keynote-189 who received pembrolizumab in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (hazard ratio, 0.49 [95% confidence interval, 0.38-0.64]; P less than .00001), according to the company press statement.

There was also a significant improvement in progression-free survival (PFS) with the pembrolizumab plus chemotherapy combination, compared with chemotherapy alone (HR, 0.52 [95% CI, 0.43-0.64]; P less than .00001).

Patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for four cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or cisplatin or carboplatin and pemetrexed intravenously every 3 weeks for four cycles followed by pemetrexed every 3 weeks (n = 206). Treatment continued until progression of disease or unacceptable toxicity.

The most common adverse reactions with pembrolizumab, resulting in discontinuation, were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions or laboratory abnormalities resulting in interruption of treatment were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%).

The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo) for treating patients with metastatic small-cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.

Approval was based on an overall response rate and duration of response in the monotherapy arm of the multicohort phase 1/2 CheckMate 032 trial. Of 109 patients with SCLC and progression after at least one previous platinum-containing regimen, 12% responded to monotherapy treatment with nivolumab regardless of PD-L1 status, 12 patients had a partial response, and one patient had a complete response.

Among responders, the median duration of response was 17.9 months. Results of the trial were presented at the ASCO annual meeting and published online in The Lancet Oncology in 2016.

Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.

The approved dose is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity, the company said in a press statement announcing the approval.

The checkpoint inhibitor was approved for treating patients with metastatic non–small-cell lung cancer with progression on or after platinum-based chemotherapy in 2015.

lnikolaides@mdedge.com

The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo) for treating patients with metastatic small-cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.

Approval was based on an overall response rate and duration of response in the monotherapy arm of the multicohort phase 1/2 CheckMate 032 trial. Of 109 patients with SCLC and progression after at least one previous platinum-containing regimen, 12% responded to monotherapy treatment with nivolumab regardless of PD-L1 status, 12 patients had a partial response, and one patient had a complete response.

Among responders, the median duration of response was 17.9 months. Results of the trial were presented at the ASCO annual meeting and published online in The Lancet Oncology in 2016.

Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.

The approved dose is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity, the company said in a press statement announcing the approval.

The checkpoint inhibitor was approved for treating patients with metastatic non–small-cell lung cancer with progression on or after platinum-based chemotherapy in 2015.

lnikolaides@mdedge.com

The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo) for treating patients with metastatic small-cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.

Approval was based on an overall response rate and duration of response in the monotherapy arm of the multicohort phase 1/2 CheckMate 032 trial. Of 109 patients with SCLC and progression after at least one previous platinum-containing regimen, 12% responded to monotherapy treatment with nivolumab regardless of PD-L1 status, 12 patients had a partial response, and one patient had a complete response.

Among responders, the median duration of response was 17.9 months. Results of the trial were presented at the ASCO annual meeting and published online in The Lancet Oncology in 2016.

Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.

The approved dose is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity, the company said in a press statement announcing the approval.

The checkpoint inhibitor was approved for treating patients with metastatic non–small-cell lung cancer with progression on or after platinum-based chemotherapy in 2015.

lnikolaides@mdedge.com

Compared with patients who underwent drainage for treatment of symptomatic malignant pleural effusions that was guided by symptoms, patients who underwent once-daily drainage had similar breathless scores but an increased rate of spontaneous pleurodesis and better quality of life scores, according to recent research published in the Lancet Respiratory Medicine.

Nephron/Wikimedia Commons/CC-BY-SA-3.0

“In patients in whom pleurodesis is an important goal (e.g., those undertaking strategies involving an indwelling pleural catheter plus pleurodesing agents), aggressive drainage should be done for at least 60 days,” Sanjeevan Muruganandan, FRACP, MBBS, from Sir Charles Gairdner Hospital in Perth, Australia, and his colleagues wrote in their study. “Future studies will need to establish if more aggressive (e.g., twice daily) regimens for the initial phase could further enhance success rates.”

Dr. Muruganandan and his colleagues evaluated 87 patients with symptomatic malignant pleural effusions between July 2015 and January 2017 from 11 centers in Australia, New Zealand, Hong Kong, and Malaysia in the randomized controlled AMPLE-2 trial, in which patients received either once daily (43 patients) or symptom-guided (44 patients) drainage for 60 days with a 6-month follow-up. Patients were excluded if they had a pleural infection, were pregnant, had a previous pneumonectomy or ipsilateral lobectomy, had “significant loculations likely to preclude effective fluid drainage,” or had an estimated survival of less than 3 months. Patients were identified and grouped based on whether they had mesothelioma- or nonmesothelioma-type cancer, with cancer type being minimalized during randomization.

At 60 days, patients in the aggressive daily drainage group had a mean daily breathless score of 13.1 mm (geometric means; 95% confidence interval, 9.8-17.4), compared with a mean of 17.3 mm (95% CI, 13.0-22.0) in the symptom-guided drainage group. In the aggressive drainage group, 16 of 43 patients (37.2%) achieved spontaneous pleurodesis at 60 days, compared with 11 of 44 patients (11.4%) in the symptom-guided drainage group (P = .0049). At 6 months, 19 of 43 (44.2%) patients in the aggressive drainage group had spontaneous pleurodesis, compared with 7 of 44 patients (15.9%; P = .004) in the symptom-guided drainage group (hazard ratio, 3.287; 95% CI, 1.396-7.740; P = .0065).

In each group, the investigators noted adverse events: 11 of 43 (25.6%) patients in the aggressive drainage group and 12 of 44 patients (27.3%) in the symptom-guided drainage group reported a severe adverse event. There were no significant differences in mortality, pain scores, and hospital stay between the groups. Regarding quality of life, the investigators found patients in the aggressive drainage group reported better scores using the EuroQoL-5 Dimensions-5 Levels assessment (estimated means, 0.713; 95% CI, 0.647-0.779) than did patients in the symptom-guided group (0.601; 95% CI, 0.536-0.667), with an estimated difference in means of 0.112 (95% CI, 0.0198-0.204; P = .0174).

The investigators suggested that aggressive drainage may have some unmeasured benefits. “Daily removal of the fluid might have provided benefits in symptoms not captured with our breathlessness and pain measurements. The higher pleurodesis rate, with resultant freedom from fluid (and symptom) recurrence and of the catheter, might have contributed to the better reported quality of life. Additionally, it has been suggested that indwelling pleural catheter drainage gives patients an important sense of control when they are feeling helpless with their advancing cancer.”

They concluded, “For patients whose primary care aim is palliation (e.g., those with very limited life expectancy or significant trapped lung where pleurodesis is unlikely), our data show that symptom-guided drainage offers an effective means of breathlessness control without the inconvenience and costs of daily drainages. The ability to predict the likelihood of pleurodesis will help guide the choice of regimen and should be a topic of future studies.”

Three authors reported serving on the advisory board of CareFusion/BD, two authors reported an educational grant from Rocket Medical (UK), and one author reported an educational grant from CareFusion/BD. The other authors reported no relevant conflicts of interest.

SOURCE: Muruganandan S et al. Lancet Respir Med. 2018 July 20. doi: 10.1016/S2213-2600(18)30288-1.

Compared with patients who underwent drainage for treatment of symptomatic malignant pleural effusions that was guided by symptoms, patients who underwent once-daily drainage had similar breathless scores but an increased rate of spontaneous pleurodesis and better quality of life scores, according to recent research published in the Lancet Respiratory Medicine.

Nephron/Wikimedia Commons/CC-BY-SA-3.0

“In patients in whom pleurodesis is an important goal (e.g., those undertaking strategies involving an indwelling pleural catheter plus pleurodesing agents), aggressive drainage should be done for at least 60 days,” Sanjeevan Muruganandan, FRACP, MBBS, from Sir Charles Gairdner Hospital in Perth, Australia, and his colleagues wrote in their study. “Future studies will need to establish if more aggressive (e.g., twice daily) regimens for the initial phase could further enhance success rates.”

Dr. Muruganandan and his colleagues evaluated 87 patients with symptomatic malignant pleural effusions between July 2015 and January 2017 from 11 centers in Australia, New Zealand, Hong Kong, and Malaysia in the randomized controlled AMPLE-2 trial, in which patients received either once daily (43 patients) or symptom-guided (44 patients) drainage for 60 days with a 6-month follow-up. Patients were excluded if they had a pleural infection, were pregnant, had a previous pneumonectomy or ipsilateral lobectomy, had “significant loculations likely to preclude effective fluid drainage,” or had an estimated survival of less than 3 months. Patients were identified and grouped based on whether they had mesothelioma- or nonmesothelioma-type cancer, with cancer type being minimalized during randomization.

At 60 days, patients in the aggressive daily drainage group had a mean daily breathless score of 13.1 mm (geometric means; 95% confidence interval, 9.8-17.4), compared with a mean of 17.3 mm (95% CI, 13.0-22.0) in the symptom-guided drainage group. In the aggressive drainage group, 16 of 43 patients (37.2%) achieved spontaneous pleurodesis at 60 days, compared with 11 of 44 patients (11.4%) in the symptom-guided drainage group (P = .0049). At 6 months, 19 of 43 (44.2%) patients in the aggressive drainage group had spontaneous pleurodesis, compared with 7 of 44 patients (15.9%; P = .004) in the symptom-guided drainage group (hazard ratio, 3.287; 95% CI, 1.396-7.740; P = .0065).

In each group, the investigators noted adverse events: 11 of 43 (25.6%) patients in the aggressive drainage group and 12 of 44 patients (27.3%) in the symptom-guided drainage group reported a severe adverse event. There were no significant differences in mortality, pain scores, and hospital stay between the groups. Regarding quality of life, the investigators found patients in the aggressive drainage group reported better scores using the EuroQoL-5 Dimensions-5 Levels assessment (estimated means, 0.713; 95% CI, 0.647-0.779) than did patients in the symptom-guided group (0.601; 95% CI, 0.536-0.667), with an estimated difference in means of 0.112 (95% CI, 0.0198-0.204; P = .0174).

The investigators suggested that aggressive drainage may have some unmeasured benefits. “Daily removal of the fluid might have provided benefits in symptoms not captured with our breathlessness and pain measurements. The higher pleurodesis rate, with resultant freedom from fluid (and symptom) recurrence and of the catheter, might have contributed to the better reported quality of life. Additionally, it has been suggested that indwelling pleural catheter drainage gives patients an important sense of control when they are feeling helpless with their advancing cancer.”

They concluded, “For patients whose primary care aim is palliation (e.g., those with very limited life expectancy or significant trapped lung where pleurodesis is unlikely), our data show that symptom-guided drainage offers an effective means of breathlessness control without the inconvenience and costs of daily drainages. The ability to predict the likelihood of pleurodesis will help guide the choice of regimen and should be a topic of future studies.”

Three authors reported serving on the advisory board of CareFusion/BD, two authors reported an educational grant from Rocket Medical (UK), and one author reported an educational grant from CareFusion/BD. The other authors reported no relevant conflicts of interest.

SOURCE: Muruganandan S et al. Lancet Respir Med. 2018 July 20. doi: 10.1016/S2213-2600(18)30288-1.

Compared with patients who underwent drainage for treatment of symptomatic malignant pleural effusions that was guided by symptoms, patients who underwent once-daily drainage had similar breathless scores but an increased rate of spontaneous pleurodesis and better quality of life scores, according to recent research published in the Lancet Respiratory Medicine.

Nephron/Wikimedia Commons/CC-BY-SA-3.0

“In patients in whom pleurodesis is an important goal (e.g., those undertaking strategies involving an indwelling pleural catheter plus pleurodesing agents), aggressive drainage should be done for at least 60 days,” Sanjeevan Muruganandan, FRACP, MBBS, from Sir Charles Gairdner Hospital in Perth, Australia, and his colleagues wrote in their study. “Future studies will need to establish if more aggressive (e.g., twice daily) regimens for the initial phase could further enhance success rates.”

Dr. Muruganandan and his colleagues evaluated 87 patients with symptomatic malignant pleural effusions between July 2015 and January 2017 from 11 centers in Australia, New Zealand, Hong Kong, and Malaysia in the randomized controlled AMPLE-2 trial, in which patients received either once daily (43 patients) or symptom-guided (44 patients) drainage for 60 days with a 6-month follow-up. Patients were excluded if they had a pleural infection, were pregnant, had a previous pneumonectomy or ipsilateral lobectomy, had “significant loculations likely to preclude effective fluid drainage,” or had an estimated survival of less than 3 months. Patients were identified and grouped based on whether they had mesothelioma- or nonmesothelioma-type cancer, with cancer type being minimalized during randomization.

At 60 days, patients in the aggressive daily drainage group had a mean daily breathless score of 13.1 mm (geometric means; 95% confidence interval, 9.8-17.4), compared with a mean of 17.3 mm (95% CI, 13.0-22.0) in the symptom-guided drainage group. In the aggressive drainage group, 16 of 43 patients (37.2%) achieved spontaneous pleurodesis at 60 days, compared with 11 of 44 patients (11.4%) in the symptom-guided drainage group (P = .0049). At 6 months, 19 of 43 (44.2%) patients in the aggressive drainage group had spontaneous pleurodesis, compared with 7 of 44 patients (15.9%; P = .004) in the symptom-guided drainage group (hazard ratio, 3.287; 95% CI, 1.396-7.740; P = .0065).

In each group, the investigators noted adverse events: 11 of 43 (25.6%) patients in the aggressive drainage group and 12 of 44 patients (27.3%) in the symptom-guided drainage group reported a severe adverse event. There were no significant differences in mortality, pain scores, and hospital stay between the groups. Regarding quality of life, the investigators found patients in the aggressive drainage group reported better scores using the EuroQoL-5 Dimensions-5 Levels assessment (estimated means, 0.713; 95% CI, 0.647-0.779) than did patients in the symptom-guided group (0.601; 95% CI, 0.536-0.667), with an estimated difference in means of 0.112 (95% CI, 0.0198-0.204; P = .0174).

The investigators suggested that aggressive drainage may have some unmeasured benefits. “Daily removal of the fluid might have provided benefits in symptoms not captured with our breathlessness and pain measurements. The higher pleurodesis rate, with resultant freedom from fluid (and symptom) recurrence and of the catheter, might have contributed to the better reported quality of life. Additionally, it has been suggested that indwelling pleural catheter drainage gives patients an important sense of control when they are feeling helpless with their advancing cancer.”

They concluded, “For patients whose primary care aim is palliation (e.g., those with very limited life expectancy or significant trapped lung where pleurodesis is unlikely), our data show that symptom-guided drainage offers an effective means of breathlessness control without the inconvenience and costs of daily drainages. The ability to predict the likelihood of pleurodesis will help guide the choice of regimen and should be a topic of future studies.”

Three authors reported serving on the advisory board of CareFusion/BD, two authors reported an educational grant from Rocket Medical (UK), and one author reported an educational grant from CareFusion/BD. The other authors reported no relevant conflicts of interest.

SOURCE: Muruganandan S et al. Lancet Respir Med. 2018 July 20. doi: 10.1016/S2213-2600(18)30288-1.

Early detection of small cell lung cancer by low-dose CT had no significant impact on patient survival, based on data from a randomized trial.

windcatcher/Thinkstock.com

Although early detection of small-cell lung cancer might improve outcomes for patients given the metastatic nature of the disease, previous studies on the value and impact of low-dose CT have been divergent, wrote Anish Thomas, MD, of the National Cancer Institute and his colleagues.

In a study published in Chest, the researchers reviewed characteristics of low-dose CT–detected small cell lung cancer (SCLC) in the randomized National Lung Screening Trial (NLST). The trial compared low-dose CT (LDCT) with chest radiography to assess patients at high risk for developing lung cancer. The study population included adults aged 55-74 years with a history of smoking of at least 30 pack-years, and former smokers who had quit within the past 15 years.

A total of 26,722 participants were randomized to the LDCT treatment arm with a median follow-up of 6.5 years; 143 SCLC cases and 926 non–small cell lung cancer (NSCLC) cases were identified in this group.

Of the 143 SCLC cases, 49 (34.2%) were screen detected, 15 (10.5%) were interval detected and 79 (55.2%) were not screened or were identified post screening.

A cancer was defined as screen detected if it was diagnosed within 1 year of a positive screening or diagnosed after a longer period but with no time gap between diagnostic procedures of more than 1 year; an interval cancer was diagnosed within a year of a negative screen, and non-screened cancers were those found in patients who received no NLST screening or other post screening.

Significantly more of the SCLC cases were at stage III or IV than the NSCLC cases (86% vs. 36%). Unfavorable stage III or IV lung cancers were identified in 80% of screen detected, 86% of interval detected, and 90% of nonscreened or postscreened cases.

In addition, 31 (63%) of the 49 screen-detected SCLC cases had at least one noncalcified nodule in the cancer lobe and 24 (49%) had a single NCN in the cancer lobe.

The 3-year cancer-specific survival rates were not significantly different for screen-detected, interval-detected, and nonscreened or postscreened cases (15.3%, 20.0%, and 13.8%, respectively).

“As expected, the majority of SCLC were late-stage cancers, but surprisingly the unfavorable stage distribution was present regardless of whether the cancer was screen-, interval- or post-screen detected,” the researchers noted.

The findings differed from the results of previous smaller studies showing more favorable stage distribution for SCLC cases detected by LDCT, but this difference may be accounted for by various factors including study populations that were smaller, younger, and lacking well-defined risk factors, the researchers said.

“Our findings underscore and provide further granularity to the premise that SCLC is a very aggressive neoplasm, and contrary to smaller prior studies, indicate that LDCT is an ineffective tool to screen for SCLC,” they said. “If early detection of SCLC were to be realistic, it would need to be detected before [lesions] are visible on LDCT,” they emphasized.

The study was supported in part by the National Cancer Institute. The researchers had no financial conflicts to disclose.

SOURCE: Thomas A et al. Chest. 2018 Aug 3. doi: 10.1016/j.chest.2018.07.029.

Early detection of small cell lung cancer by low-dose CT had no significant impact on patient survival, based on data from a randomized trial.

windcatcher/Thinkstock.com

Although early detection of small-cell lung cancer might improve outcomes for patients given the metastatic nature of the disease, previous studies on the value and impact of low-dose CT have been divergent, wrote Anish Thomas, MD, of the National Cancer Institute and his colleagues.

In a study published in Chest, the researchers reviewed characteristics of low-dose CT–detected small cell lung cancer (SCLC) in the randomized National Lung Screening Trial (NLST). The trial compared low-dose CT (LDCT) with chest radiography to assess patients at high risk for developing lung cancer. The study population included adults aged 55-74 years with a history of smoking of at least 30 pack-years, and former smokers who had quit within the past 15 years.

A total of 26,722 participants were randomized to the LDCT treatment arm with a median follow-up of 6.5 years; 143 SCLC cases and 926 non–small cell lung cancer (NSCLC) cases were identified in this group.

Of the 143 SCLC cases, 49 (34.2%) were screen detected, 15 (10.5%) were interval detected and 79 (55.2%) were not screened or were identified post screening.

A cancer was defined as screen detected if it was diagnosed within 1 year of a positive screening or diagnosed after a longer period but with no time gap between diagnostic procedures of more than 1 year; an interval cancer was diagnosed within a year of a negative screen, and non-screened cancers were those found in patients who received no NLST screening or other post screening.

Significantly more of the SCLC cases were at stage III or IV than the NSCLC cases (86% vs. 36%). Unfavorable stage III or IV lung cancers were identified in 80% of screen detected, 86% of interval detected, and 90% of nonscreened or postscreened cases.

In addition, 31 (63%) of the 49 screen-detected SCLC cases had at least one noncalcified nodule in the cancer lobe and 24 (49%) had a single NCN in the cancer lobe.

The 3-year cancer-specific survival rates were not significantly different for screen-detected, interval-detected, and nonscreened or postscreened cases (15.3%, 20.0%, and 13.8%, respectively).

“As expected, the majority of SCLC were late-stage cancers, but surprisingly the unfavorable stage distribution was present regardless of whether the cancer was screen-, interval- or post-screen detected,” the researchers noted.

The findings differed from the results of previous smaller studies showing more favorable stage distribution for SCLC cases detected by LDCT, but this difference may be accounted for by various factors including study populations that were smaller, younger, and lacking well-defined risk factors, the researchers said.

“Our findings underscore and provide further granularity to the premise that SCLC is a very aggressive neoplasm, and contrary to smaller prior studies, indicate that LDCT is an ineffective tool to screen for SCLC,” they said. “If early detection of SCLC were to be realistic, it would need to be detected before [lesions] are visible on LDCT,” they emphasized.

The study was supported in part by the National Cancer Institute. The researchers had no financial conflicts to disclose.

SOURCE: Thomas A et al. Chest. 2018 Aug 3. doi: 10.1016/j.chest.2018.07.029.

Early detection of small cell lung cancer by low-dose CT had no significant impact on patient survival, based on data from a randomized trial.

windcatcher/Thinkstock.com

Although early detection of small-cell lung cancer might improve outcomes for patients given the metastatic nature of the disease, previous studies on the value and impact of low-dose CT have been divergent, wrote Anish Thomas, MD, of the National Cancer Institute and his colleagues.

In a study published in Chest, the researchers reviewed characteristics of low-dose CT–detected small cell lung cancer (SCLC) in the randomized National Lung Screening Trial (NLST). The trial compared low-dose CT (LDCT) with chest radiography to assess patients at high risk for developing lung cancer. The study population included adults aged 55-74 years with a history of smoking of at least 30 pack-years, and former smokers who had quit within the past 15 years.

A total of 26,722 participants were randomized to the LDCT treatment arm with a median follow-up of 6.5 years; 143 SCLC cases and 926 non–small cell lung cancer (NSCLC) cases were identified in this group.

Of the 143 SCLC cases, 49 (34.2%) were screen detected, 15 (10.5%) were interval detected and 79 (55.2%) were not screened or were identified post screening.

A cancer was defined as screen detected if it was diagnosed within 1 year of a positive screening or diagnosed after a longer period but with no time gap between diagnostic procedures of more than 1 year; an interval cancer was diagnosed within a year of a negative screen, and non-screened cancers were those found in patients who received no NLST screening or other post screening.

Significantly more of the SCLC cases were at stage III or IV than the NSCLC cases (86% vs. 36%). Unfavorable stage III or IV lung cancers were identified in 80% of screen detected, 86% of interval detected, and 90% of nonscreened or postscreened cases.

In addition, 31 (63%) of the 49 screen-detected SCLC cases had at least one noncalcified nodule in the cancer lobe and 24 (49%) had a single NCN in the cancer lobe.

The 3-year cancer-specific survival rates were not significantly different for screen-detected, interval-detected, and nonscreened or postscreened cases (15.3%, 20.0%, and 13.8%, respectively).

“As expected, the majority of SCLC were late-stage cancers, but surprisingly the unfavorable stage distribution was present regardless of whether the cancer was screen-, interval- or post-screen detected,” the researchers noted.

The findings differed from the results of previous smaller studies showing more favorable stage distribution for SCLC cases detected by LDCT, but this difference may be accounted for by various factors including study populations that were smaller, younger, and lacking well-defined risk factors, the researchers said.

“Our findings underscore and provide further granularity to the premise that SCLC is a very aggressive neoplasm, and contrary to smaller prior studies, indicate that LDCT is an ineffective tool to screen for SCLC,” they said. “If early detection of SCLC were to be realistic, it would need to be detected before [lesions] are visible on LDCT,” they emphasized.

The study was supported in part by the National Cancer Institute. The researchers had no financial conflicts to disclose.

SOURCE: Thomas A et al. Chest. 2018 Aug 3. doi: 10.1016/j.chest.2018.07.029.

A small study of discussions between clinicians and patients about lung cancer screening with low-dose computed tomography has highlighted a lack of shared decision making and information about potential harms.

“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.

The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).

Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.

Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).

“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.

The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.

“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”

Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.

“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”

The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.

SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.

A small study of discussions between clinicians and patients about lung cancer screening with low-dose computed tomography has highlighted a lack of shared decision making and information about potential harms.

“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.

The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).

Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.

Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).

“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.

The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.

“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”

Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.

“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”

The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.

SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.

A small study of discussions between clinicians and patients about lung cancer screening with low-dose computed tomography has highlighted a lack of shared decision making and information about potential harms.

“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.

The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).

Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.

Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).

“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.

The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.

“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”

Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.

“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”

The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.

SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.