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Adagrasib shows durable benefit in KRAS-mutated NSCLC
with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.
“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.
“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.
New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.
Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.
If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.
Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
Published clinical data
The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.
It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.
Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.
On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.
Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.
Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.
“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.
Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
CNS metastases
At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.
As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.
The study was funded by Mirati Therapeutics.
A version of this article first appeared on Medscape.com.
with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.
“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.
“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.
New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.
Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.
If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.
Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
Published clinical data
The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.
It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.
Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.
On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.
Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.
Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.
“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.
Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
CNS metastases
At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.
As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.
The study was funded by Mirati Therapeutics.
A version of this article first appeared on Medscape.com.
with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.
“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.
“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.
New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.
Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.
If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.
Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
Published clinical data
The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.
It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.
Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.
On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.
Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.
Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.
“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.
Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
CNS metastases
At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.
As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.
The study was funded by Mirati Therapeutics.
A version of this article first appeared on Medscape.com.
FROM ASCO 2022
Immunotherapy treatment combo charts new course for resectable NSCLC treatment
Among patients with resectable non–small cell lung cancer (NSCLC), and more frequent pathological complete response in patients than chemotherapy alone.
“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.
Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.
About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.
In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
Results from CheckMate 816
CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.
Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.
After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).
A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).
Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.
The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.
There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.
The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.
Among patients with resectable non–small cell lung cancer (NSCLC), and more frequent pathological complete response in patients than chemotherapy alone.
“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.
Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.
About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.
In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
Results from CheckMate 816
CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.
Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.
After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).
A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).
Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.
The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.
There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.
The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.
Among patients with resectable non–small cell lung cancer (NSCLC), and more frequent pathological complete response in patients than chemotherapy alone.
“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.
Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.
About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.
In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
Results from CheckMate 816
CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.
Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.
After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).
A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).
Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.
The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.
There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.
The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Commentary: Genetic Components of NSCLC, June 2022
Real-World Retrospective Study Suggests Inferior Outcomes to First-Line Systemic Treatment in Advanced NFE2L2 and KEAP1 Mutant Squamous NSCLC
Targeted therapies against oncogene-driven lung cancer, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), in lung adenocarcinoma have revolutionized lung cancer treatment. However, there are no US Food and Drug Administration–approved targeted therapies for commonly occurring mutations in advanced squamous non–small cell lung cancer (NSCLC).
NFE2L2 and KEAP1 mutations are molecular alterations that occur in about 25%-30% of squamous NSCLC. NFE2L2 encodes for the NRF2 transcription factor that is involved in the oxidative stress pathway and KEAP1 encodes for the KEAP1 protein, which is the negative regulator of NFE2L2.1 When the NRF2-KEAP1 signaling pathway is disrupted, there is persistent activation of NRF2, which promotes cell proliferation and carcinogenesis and may contribute to resistance to cancer-directed treatments. Previous retrospective studies suggest that patients with lung cancers harboring NFE2L2 and KEAP1 mutations have a poorer prognosis and do worse with both systemic anticancer treatments and radiation.2-5
Wu and colleagues, in a retrospective cohort study, identified 703 patients with squamous NSCLC from 2011 to 2018 who had NFE2L2 or KEAP1 mutations identified by comprehensive genomic profiling in the Flatiron Health-Foundation Medicine Clinico-Genomic Database. Real-world progression-free survival (PFS), defined as a distinct episode where the clinician concluded that there was growth or worsening of disease, was assessed by line and type of treatment, as was overall survival (OS). Patients with squamous NSCLC with NFE2L2/KEAP1 mutations had shorter real-world PFS to first-line treatment compared with patients whose tumors were wild-type for these mutations (4.54 months vs 6.25 months; P = .0027). Median OS was numerically shorter in patients with NFE2L2/KEAP1 mutations, but this was not statistically significant (13.59 vs 17.37 months; P = .41). This retrospective real-world analysis suggests that patients with squamous NSCLC and NFE2L2/KEAP1 mutations have inferior outcomes with systemic treatments and may have worsened OS; however, this was not statistically significant. Many of these patients were treated before the approval of the KEYNOTE-407 chemo-immunotherapy regimen in squamous NSCLC, so they did not have what we would consider contemporary standard treatment. Further studies are needed to evaluate the role of NRF2 activation in resistance to NSCLC treatments, and there is a need for therapeutics to target these common mutations in squamous NSCLC. Fortunately, there are current ongoing clinical trials.[6]
Segmentectomy Is Noninferior to and Improves Overall Survival Compared With Lobectomy in Selected Cases of Small Peripheral Early-Stage NSCLC
Lobectomy has been the standard of care for surgical treatment of early-stage NSCLC. Saji and colleagues investigated whether segmentectomy was noninferior to lobectomy in selected cases of small-sized peripheral NSCLC. This randomized, controlled, noninferiority trial was conducted at 70 institutions in Japan.
Patients with selected stage IA (American Joint Committee on Cancer [AJCC], seventh edition) NSCLC (peripheral tumors, £ 2 cm diameter, consolidation-to-tumor ratio > 0.5) were randomly assigned to undergo segmentectomy or lobectomy. The primary endpoint was OS. Pertinent secondary endpoints included postoperative respiratory function, relapse-free survival, and adverse events.
A total of 1106 patients were enrolled: 554 in the lobectomy group and 552 in the segmentectomy group. The 5-year OS was 94.3% for segmentectomy and 91.1% for lobectomy (hazard ratio 0.663; one-sided P < .001 for noninferiority; P = .0082 for superiority). In addition to the modestly improved OS observed, 5-year relapse-free survival was comparable between the groups (88% for segmentectomy and 87.9% for lobectomy). However, more local relapse was observed for segmentectomy (10.5%) than for lobectomy (5.4%) (P = .0018). Despite significantly more locoregional recurrences with segmentectomy compared with lobectomy, rates of combined distant and locoregional relapses were similar. Slightly more patients died in the lobectomy group than the segmentectomy group, and the rate of cancer-related deaths, including second primary lung cancers, was higher in the lobectomy group. Interestingly, although segmentectomy had better OS, the survival advantage was not cancer-specific.
The mechanism by which segmentectomy improved survival over lobectomy in these selected patients with small, peripheral stage IA NSCLC is still unclear. Limitations of the study included that all patients were from one geographic region (Japan) and that the study was unblinded, which can introduce bias. We await the results of CALGB 140503: A Randomized Phase III Trial of Lobectomy versus Sublobar Resection for Small (< 2cm) Peripheral Non-Small Cell Lung Cancer (NCT00499330). This study is being done in a US population and includes nonanatomic wedge in its sublobar resection cohort.
The study by Saji and colleagues suggests that surgeons should consider segmentectomy in appropriate patients (select small stage IA NSCLC [peripheral tumors, £ 2 cm diameter, consolidation-to-tumor ratio > 0.5]), based on the modest improvement in OS compared with lobectomy.
Immunotherapy Activity in Cachexic and Noncachexic Patients With Advanced NSCLC and Clinical Outcomes, by Adipose Tissue Loss on Treatment
There are emerging data that body mass index (BMI) and the presence or absence of cachexia in cancers, including NSCLC, may change the efficacy of programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors. Nishioka and colleagues, in a single-center retrospective cohort, examined patients with advanced NSCLC (40 with cachexia and 34 without cachexia) who received PD-L1 inhibitors (pembrolizumab, nivolumab, or atezolizumab). Patients were excluded if they had poor performance status, EGFR/ALK/ROS1 oncogene drivers, unknown PD-L1 expression status, and unknown weight loss in the 6 months before immunotherapy administration. In addition to BMI, measurements of adipose tissue quantity and muscle mass were used.
The overall response rate was 28.4% in the 74 patients analyzed. Patients with cachexia had a lower overall response rate than those without cachexia (15.0% vs 44.1%; P < .05). Among the patients without cachexia, those with total adipose tissue loss had a significantly longer PFS than those with total adipose tissue maintenance (18.5 months vs 2.86 months; P = .037), including in a multivariate analyses (hazard ratio 0.34; P < .05), after adjustment for PD-L1 expression and performance status (Eastern Cooperative Oncology Group [ECOG] 0 vs. 1).
Mechanistically, a paradoxical effect of obesity on T-cell function that relates to leptin, which is secreted by adipose tissue, has been observed in preclinical studies.7 In a previously published study, obesity resulted in tumor progression and PD-1–mediated T-cell dysfunction, which can be overcome by PD-L1 blockade with improved clinical outcomes to these therapies in patients with obesity and cancer, including NSCLC.7 This "obesity paradox" may underlie some of the findings observed in Nishioka and colleagues' study. More research needs to be done regarding the activity of immune checkpoint inhibition in NSCLC as it relates to BMI, cachexia, and amount of adipose tissue.
Additional References
1. Shibata T, Ohta T, Tong KI, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008;105(36):13568-13573. doi: 10.1073/pnas.0806268105
2. Frank R, Scheffler M, Merkelbach-Bruse S, et al. Clinical and pathological characteristics of KEAP1- and NFE2L2-mutated non-small cell lung carcinoma (NSCLC). Clin Cancer Res. 2018;24:3087-3096. doi: 10.1158/1078-0432.CCR-17-3416
3. Binkley MS, Jeon YJ, Nesselbush M, et al. KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer Discov. 2020;10(12):1826-1841. doi: 10.1158/2159-8290.CD-20-0282
4. Hellyer JA, Padda SK, Diehn M, et al. Clinical implications of KEAP1-NFE2L2 mutations in NSCLC. J Thorac Oncol. 2021;16(3):395-403. doi: 10.1016/j.jtho.2020.11.015
5. Jeong Y, Hellyer JA, Stehr H, et al. Role of KEAP1/NFE2L2 mutations in the chemotherapeutic response of patients with non-small cell lung cancer. Clin Cancer Res. 2020;26(1):274-281. doi: 10.1158/1078-0432.CCR-19-1237
6. Riess JW, Frankel P, Shackelford D, et al. Phase 1 trial of MLN0128 (sapanisertib) and CB-839 HCl (telaglenastat) in patients with advanced NSCLC (NCI 10327): Rationale and study design. Clin Lung Cancer. 2021;22:67-70. doi: 10.1016/j.cllc.2020.10.006
Real-World Retrospective Study Suggests Inferior Outcomes to First-Line Systemic Treatment in Advanced NFE2L2 and KEAP1 Mutant Squamous NSCLC
Targeted therapies against oncogene-driven lung cancer, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), in lung adenocarcinoma have revolutionized lung cancer treatment. However, there are no US Food and Drug Administration–approved targeted therapies for commonly occurring mutations in advanced squamous non–small cell lung cancer (NSCLC).
NFE2L2 and KEAP1 mutations are molecular alterations that occur in about 25%-30% of squamous NSCLC. NFE2L2 encodes for the NRF2 transcription factor that is involved in the oxidative stress pathway and KEAP1 encodes for the KEAP1 protein, which is the negative regulator of NFE2L2.1 When the NRF2-KEAP1 signaling pathway is disrupted, there is persistent activation of NRF2, which promotes cell proliferation and carcinogenesis and may contribute to resistance to cancer-directed treatments. Previous retrospective studies suggest that patients with lung cancers harboring NFE2L2 and KEAP1 mutations have a poorer prognosis and do worse with both systemic anticancer treatments and radiation.2-5
Wu and colleagues, in a retrospective cohort study, identified 703 patients with squamous NSCLC from 2011 to 2018 who had NFE2L2 or KEAP1 mutations identified by comprehensive genomic profiling in the Flatiron Health-Foundation Medicine Clinico-Genomic Database. Real-world progression-free survival (PFS), defined as a distinct episode where the clinician concluded that there was growth or worsening of disease, was assessed by line and type of treatment, as was overall survival (OS). Patients with squamous NSCLC with NFE2L2/KEAP1 mutations had shorter real-world PFS to first-line treatment compared with patients whose tumors were wild-type for these mutations (4.54 months vs 6.25 months; P = .0027). Median OS was numerically shorter in patients with NFE2L2/KEAP1 mutations, but this was not statistically significant (13.59 vs 17.37 months; P = .41). This retrospective real-world analysis suggests that patients with squamous NSCLC and NFE2L2/KEAP1 mutations have inferior outcomes with systemic treatments and may have worsened OS; however, this was not statistically significant. Many of these patients were treated before the approval of the KEYNOTE-407 chemo-immunotherapy regimen in squamous NSCLC, so they did not have what we would consider contemporary standard treatment. Further studies are needed to evaluate the role of NRF2 activation in resistance to NSCLC treatments, and there is a need for therapeutics to target these common mutations in squamous NSCLC. Fortunately, there are current ongoing clinical trials.[6]
Segmentectomy Is Noninferior to and Improves Overall Survival Compared With Lobectomy in Selected Cases of Small Peripheral Early-Stage NSCLC
Lobectomy has been the standard of care for surgical treatment of early-stage NSCLC. Saji and colleagues investigated whether segmentectomy was noninferior to lobectomy in selected cases of small-sized peripheral NSCLC. This randomized, controlled, noninferiority trial was conducted at 70 institutions in Japan.
Patients with selected stage IA (American Joint Committee on Cancer [AJCC], seventh edition) NSCLC (peripheral tumors, £ 2 cm diameter, consolidation-to-tumor ratio > 0.5) were randomly assigned to undergo segmentectomy or lobectomy. The primary endpoint was OS. Pertinent secondary endpoints included postoperative respiratory function, relapse-free survival, and adverse events.
A total of 1106 patients were enrolled: 554 in the lobectomy group and 552 in the segmentectomy group. The 5-year OS was 94.3% for segmentectomy and 91.1% for lobectomy (hazard ratio 0.663; one-sided P < .001 for noninferiority; P = .0082 for superiority). In addition to the modestly improved OS observed, 5-year relapse-free survival was comparable between the groups (88% for segmentectomy and 87.9% for lobectomy). However, more local relapse was observed for segmentectomy (10.5%) than for lobectomy (5.4%) (P = .0018). Despite significantly more locoregional recurrences with segmentectomy compared with lobectomy, rates of combined distant and locoregional relapses were similar. Slightly more patients died in the lobectomy group than the segmentectomy group, and the rate of cancer-related deaths, including second primary lung cancers, was higher in the lobectomy group. Interestingly, although segmentectomy had better OS, the survival advantage was not cancer-specific.
The mechanism by which segmentectomy improved survival over lobectomy in these selected patients with small, peripheral stage IA NSCLC is still unclear. Limitations of the study included that all patients were from one geographic region (Japan) and that the study was unblinded, which can introduce bias. We await the results of CALGB 140503: A Randomized Phase III Trial of Lobectomy versus Sublobar Resection for Small (< 2cm) Peripheral Non-Small Cell Lung Cancer (NCT00499330). This study is being done in a US population and includes nonanatomic wedge in its sublobar resection cohort.
The study by Saji and colleagues suggests that surgeons should consider segmentectomy in appropriate patients (select small stage IA NSCLC [peripheral tumors, £ 2 cm diameter, consolidation-to-tumor ratio > 0.5]), based on the modest improvement in OS compared with lobectomy.
Immunotherapy Activity in Cachexic and Noncachexic Patients With Advanced NSCLC and Clinical Outcomes, by Adipose Tissue Loss on Treatment
There are emerging data that body mass index (BMI) and the presence or absence of cachexia in cancers, including NSCLC, may change the efficacy of programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors. Nishioka and colleagues, in a single-center retrospective cohort, examined patients with advanced NSCLC (40 with cachexia and 34 without cachexia) who received PD-L1 inhibitors (pembrolizumab, nivolumab, or atezolizumab). Patients were excluded if they had poor performance status, EGFR/ALK/ROS1 oncogene drivers, unknown PD-L1 expression status, and unknown weight loss in the 6 months before immunotherapy administration. In addition to BMI, measurements of adipose tissue quantity and muscle mass were used.
The overall response rate was 28.4% in the 74 patients analyzed. Patients with cachexia had a lower overall response rate than those without cachexia (15.0% vs 44.1%; P < .05). Among the patients without cachexia, those with total adipose tissue loss had a significantly longer PFS than those with total adipose tissue maintenance (18.5 months vs 2.86 months; P = .037), including in a multivariate analyses (hazard ratio 0.34; P < .05), after adjustment for PD-L1 expression and performance status (Eastern Cooperative Oncology Group [ECOG] 0 vs. 1).
Mechanistically, a paradoxical effect of obesity on T-cell function that relates to leptin, which is secreted by adipose tissue, has been observed in preclinical studies.7 In a previously published study, obesity resulted in tumor progression and PD-1–mediated T-cell dysfunction, which can be overcome by PD-L1 blockade with improved clinical outcomes to these therapies in patients with obesity and cancer, including NSCLC.7 This "obesity paradox" may underlie some of the findings observed in Nishioka and colleagues' study. More research needs to be done regarding the activity of immune checkpoint inhibition in NSCLC as it relates to BMI, cachexia, and amount of adipose tissue.
Additional References
1. Shibata T, Ohta T, Tong KI, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008;105(36):13568-13573. doi: 10.1073/pnas.0806268105
2. Frank R, Scheffler M, Merkelbach-Bruse S, et al. Clinical and pathological characteristics of KEAP1- and NFE2L2-mutated non-small cell lung carcinoma (NSCLC). Clin Cancer Res. 2018;24:3087-3096. doi: 10.1158/1078-0432.CCR-17-3416
3. Binkley MS, Jeon YJ, Nesselbush M, et al. KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer Discov. 2020;10(12):1826-1841. doi: 10.1158/2159-8290.CD-20-0282
4. Hellyer JA, Padda SK, Diehn M, et al. Clinical implications of KEAP1-NFE2L2 mutations in NSCLC. J Thorac Oncol. 2021;16(3):395-403. doi: 10.1016/j.jtho.2020.11.015
5. Jeong Y, Hellyer JA, Stehr H, et al. Role of KEAP1/NFE2L2 mutations in the chemotherapeutic response of patients with non-small cell lung cancer. Clin Cancer Res. 2020;26(1):274-281. doi: 10.1158/1078-0432.CCR-19-1237
6. Riess JW, Frankel P, Shackelford D, et al. Phase 1 trial of MLN0128 (sapanisertib) and CB-839 HCl (telaglenastat) in patients with advanced NSCLC (NCI 10327): Rationale and study design. Clin Lung Cancer. 2021;22:67-70. doi: 10.1016/j.cllc.2020.10.006
Real-World Retrospective Study Suggests Inferior Outcomes to First-Line Systemic Treatment in Advanced NFE2L2 and KEAP1 Mutant Squamous NSCLC
Targeted therapies against oncogene-driven lung cancer, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), in lung adenocarcinoma have revolutionized lung cancer treatment. However, there are no US Food and Drug Administration–approved targeted therapies for commonly occurring mutations in advanced squamous non–small cell lung cancer (NSCLC).
NFE2L2 and KEAP1 mutations are molecular alterations that occur in about 25%-30% of squamous NSCLC. NFE2L2 encodes for the NRF2 transcription factor that is involved in the oxidative stress pathway and KEAP1 encodes for the KEAP1 protein, which is the negative regulator of NFE2L2.1 When the NRF2-KEAP1 signaling pathway is disrupted, there is persistent activation of NRF2, which promotes cell proliferation and carcinogenesis and may contribute to resistance to cancer-directed treatments. Previous retrospective studies suggest that patients with lung cancers harboring NFE2L2 and KEAP1 mutations have a poorer prognosis and do worse with both systemic anticancer treatments and radiation.2-5
Wu and colleagues, in a retrospective cohort study, identified 703 patients with squamous NSCLC from 2011 to 2018 who had NFE2L2 or KEAP1 mutations identified by comprehensive genomic profiling in the Flatiron Health-Foundation Medicine Clinico-Genomic Database. Real-world progression-free survival (PFS), defined as a distinct episode where the clinician concluded that there was growth or worsening of disease, was assessed by line and type of treatment, as was overall survival (OS). Patients with squamous NSCLC with NFE2L2/KEAP1 mutations had shorter real-world PFS to first-line treatment compared with patients whose tumors were wild-type for these mutations (4.54 months vs 6.25 months; P = .0027). Median OS was numerically shorter in patients with NFE2L2/KEAP1 mutations, but this was not statistically significant (13.59 vs 17.37 months; P = .41). This retrospective real-world analysis suggests that patients with squamous NSCLC and NFE2L2/KEAP1 mutations have inferior outcomes with systemic treatments and may have worsened OS; however, this was not statistically significant. Many of these patients were treated before the approval of the KEYNOTE-407 chemo-immunotherapy regimen in squamous NSCLC, so they did not have what we would consider contemporary standard treatment. Further studies are needed to evaluate the role of NRF2 activation in resistance to NSCLC treatments, and there is a need for therapeutics to target these common mutations in squamous NSCLC. Fortunately, there are current ongoing clinical trials.[6]
Segmentectomy Is Noninferior to and Improves Overall Survival Compared With Lobectomy in Selected Cases of Small Peripheral Early-Stage NSCLC
Lobectomy has been the standard of care for surgical treatment of early-stage NSCLC. Saji and colleagues investigated whether segmentectomy was noninferior to lobectomy in selected cases of small-sized peripheral NSCLC. This randomized, controlled, noninferiority trial was conducted at 70 institutions in Japan.
Patients with selected stage IA (American Joint Committee on Cancer [AJCC], seventh edition) NSCLC (peripheral tumors, £ 2 cm diameter, consolidation-to-tumor ratio > 0.5) were randomly assigned to undergo segmentectomy or lobectomy. The primary endpoint was OS. Pertinent secondary endpoints included postoperative respiratory function, relapse-free survival, and adverse events.
A total of 1106 patients were enrolled: 554 in the lobectomy group and 552 in the segmentectomy group. The 5-year OS was 94.3% for segmentectomy and 91.1% for lobectomy (hazard ratio 0.663; one-sided P < .001 for noninferiority; P = .0082 for superiority). In addition to the modestly improved OS observed, 5-year relapse-free survival was comparable between the groups (88% for segmentectomy and 87.9% for lobectomy). However, more local relapse was observed for segmentectomy (10.5%) than for lobectomy (5.4%) (P = .0018). Despite significantly more locoregional recurrences with segmentectomy compared with lobectomy, rates of combined distant and locoregional relapses were similar. Slightly more patients died in the lobectomy group than the segmentectomy group, and the rate of cancer-related deaths, including second primary lung cancers, was higher in the lobectomy group. Interestingly, although segmentectomy had better OS, the survival advantage was not cancer-specific.
The mechanism by which segmentectomy improved survival over lobectomy in these selected patients with small, peripheral stage IA NSCLC is still unclear. Limitations of the study included that all patients were from one geographic region (Japan) and that the study was unblinded, which can introduce bias. We await the results of CALGB 140503: A Randomized Phase III Trial of Lobectomy versus Sublobar Resection for Small (< 2cm) Peripheral Non-Small Cell Lung Cancer (NCT00499330). This study is being done in a US population and includes nonanatomic wedge in its sublobar resection cohort.
The study by Saji and colleagues suggests that surgeons should consider segmentectomy in appropriate patients (select small stage IA NSCLC [peripheral tumors, £ 2 cm diameter, consolidation-to-tumor ratio > 0.5]), based on the modest improvement in OS compared with lobectomy.
Immunotherapy Activity in Cachexic and Noncachexic Patients With Advanced NSCLC and Clinical Outcomes, by Adipose Tissue Loss on Treatment
There are emerging data that body mass index (BMI) and the presence or absence of cachexia in cancers, including NSCLC, may change the efficacy of programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors. Nishioka and colleagues, in a single-center retrospective cohort, examined patients with advanced NSCLC (40 with cachexia and 34 without cachexia) who received PD-L1 inhibitors (pembrolizumab, nivolumab, or atezolizumab). Patients were excluded if they had poor performance status, EGFR/ALK/ROS1 oncogene drivers, unknown PD-L1 expression status, and unknown weight loss in the 6 months before immunotherapy administration. In addition to BMI, measurements of adipose tissue quantity and muscle mass were used.
The overall response rate was 28.4% in the 74 patients analyzed. Patients with cachexia had a lower overall response rate than those without cachexia (15.0% vs 44.1%; P < .05). Among the patients without cachexia, those with total adipose tissue loss had a significantly longer PFS than those with total adipose tissue maintenance (18.5 months vs 2.86 months; P = .037), including in a multivariate analyses (hazard ratio 0.34; P < .05), after adjustment for PD-L1 expression and performance status (Eastern Cooperative Oncology Group [ECOG] 0 vs. 1).
Mechanistically, a paradoxical effect of obesity on T-cell function that relates to leptin, which is secreted by adipose tissue, has been observed in preclinical studies.7 In a previously published study, obesity resulted in tumor progression and PD-1–mediated T-cell dysfunction, which can be overcome by PD-L1 blockade with improved clinical outcomes to these therapies in patients with obesity and cancer, including NSCLC.7 This "obesity paradox" may underlie some of the findings observed in Nishioka and colleagues' study. More research needs to be done regarding the activity of immune checkpoint inhibition in NSCLC as it relates to BMI, cachexia, and amount of adipose tissue.
Additional References
1. Shibata T, Ohta T, Tong KI, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008;105(36):13568-13573. doi: 10.1073/pnas.0806268105
2. Frank R, Scheffler M, Merkelbach-Bruse S, et al. Clinical and pathological characteristics of KEAP1- and NFE2L2-mutated non-small cell lung carcinoma (NSCLC). Clin Cancer Res. 2018;24:3087-3096. doi: 10.1158/1078-0432.CCR-17-3416
3. Binkley MS, Jeon YJ, Nesselbush M, et al. KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer Discov. 2020;10(12):1826-1841. doi: 10.1158/2159-8290.CD-20-0282
4. Hellyer JA, Padda SK, Diehn M, et al. Clinical implications of KEAP1-NFE2L2 mutations in NSCLC. J Thorac Oncol. 2021;16(3):395-403. doi: 10.1016/j.jtho.2020.11.015
5. Jeong Y, Hellyer JA, Stehr H, et al. Role of KEAP1/NFE2L2 mutations in the chemotherapeutic response of patients with non-small cell lung cancer. Clin Cancer Res. 2020;26(1):274-281. doi: 10.1158/1078-0432.CCR-19-1237
6. Riess JW, Frankel P, Shackelford D, et al. Phase 1 trial of MLN0128 (sapanisertib) and CB-839 HCl (telaglenastat) in patients with advanced NSCLC (NCI 10327): Rationale and study design. Clin Lung Cancer. 2021;22:67-70. doi: 10.1016/j.cllc.2020.10.006
Using Bronchoscopy to Optimize Targeted Therapy in Non-Small Cell Lung Cancer
The expanding range of therapies and interventions available for treatment of non–small cell lung cancer (NSCLC) has brought medical oncologists and interventional pulmonologists into closer partnership.
Oncologist Dr. Joy Feliciano and interventional pulmonologist Dr. A. Christine Argento, both colleagues at Johns Hopkins University, comment on their evolving relationship as a team.
Pulmonologists now often serve as the "gatekeepers into thoracic oncology," says Dr. Argento. Recent advances in technology, including endobronchial ultrasound, navigational bronchoscopy, and robotic-assisted bronchoscopy, allow for diagnosis, staging, and collection of sufficient tissue for advanced studies into molecular markers and genetic studies necessary to guide treatment decisions for metastatic NSCLC.
In resectable disease, patients who might have gone straight to surgery in the past now can be considered for neoadjuvant treatments. Here again, says Dr. Feliciano, it is critical for oncologists to understand the biomarkers and molecular profile of the tumor before considering an intervention, and the role of bronchoscopy is key.
A multidisciplinary practice of NSCLC specialists, who have access to on-site or virtual tumor boards, sometimes on an international scale, helps ensure optimal treatment for patients in the increasingly complex NSCLC arena.
--
A. Christine Argento, MD, Associate Professor of Medicine, Department of Pulmonary and Critical Care Medicine, Johns Hopkins University; Director of Bronchoscopy, Department of Interventional Pulmonary Medicine, Johns Hopkins Hospital, Baltimore, Maryland
A. Christine Argento, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Biodesix; Olympus; Cook; Intuitive; Boston Scientific
Josephine L. Feliciano, MD, Associate Professor, Clinical Director, Sidney Kimmel Cancer Center, Johns Hopkins University Hospital, Baltimore, Maryland
Josephine L. Feliciano, MD, has disclosed the following relevant financial relationships:
Received research grant from: Bristol-Myers; Pfizer; AstraZeneca.
Received income in an amount equal to or greater than $250 from: Genentech; AstraZeneca; Eli Lilly; Merck; Regeneron; Coherus; Takeda; Bristol-Myers
The expanding range of therapies and interventions available for treatment of non–small cell lung cancer (NSCLC) has brought medical oncologists and interventional pulmonologists into closer partnership.
Oncologist Dr. Joy Feliciano and interventional pulmonologist Dr. A. Christine Argento, both colleagues at Johns Hopkins University, comment on their evolving relationship as a team.
Pulmonologists now often serve as the "gatekeepers into thoracic oncology," says Dr. Argento. Recent advances in technology, including endobronchial ultrasound, navigational bronchoscopy, and robotic-assisted bronchoscopy, allow for diagnosis, staging, and collection of sufficient tissue for advanced studies into molecular markers and genetic studies necessary to guide treatment decisions for metastatic NSCLC.
In resectable disease, patients who might have gone straight to surgery in the past now can be considered for neoadjuvant treatments. Here again, says Dr. Feliciano, it is critical for oncologists to understand the biomarkers and molecular profile of the tumor before considering an intervention, and the role of bronchoscopy is key.
A multidisciplinary practice of NSCLC specialists, who have access to on-site or virtual tumor boards, sometimes on an international scale, helps ensure optimal treatment for patients in the increasingly complex NSCLC arena.
--
A. Christine Argento, MD, Associate Professor of Medicine, Department of Pulmonary and Critical Care Medicine, Johns Hopkins University; Director of Bronchoscopy, Department of Interventional Pulmonary Medicine, Johns Hopkins Hospital, Baltimore, Maryland
A. Christine Argento, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Biodesix; Olympus; Cook; Intuitive; Boston Scientific
Josephine L. Feliciano, MD, Associate Professor, Clinical Director, Sidney Kimmel Cancer Center, Johns Hopkins University Hospital, Baltimore, Maryland
Josephine L. Feliciano, MD, has disclosed the following relevant financial relationships:
Received research grant from: Bristol-Myers; Pfizer; AstraZeneca.
Received income in an amount equal to or greater than $250 from: Genentech; AstraZeneca; Eli Lilly; Merck; Regeneron; Coherus; Takeda; Bristol-Myers
The expanding range of therapies and interventions available for treatment of non–small cell lung cancer (NSCLC) has brought medical oncologists and interventional pulmonologists into closer partnership.
Oncologist Dr. Joy Feliciano and interventional pulmonologist Dr. A. Christine Argento, both colleagues at Johns Hopkins University, comment on their evolving relationship as a team.
Pulmonologists now often serve as the "gatekeepers into thoracic oncology," says Dr. Argento. Recent advances in technology, including endobronchial ultrasound, navigational bronchoscopy, and robotic-assisted bronchoscopy, allow for diagnosis, staging, and collection of sufficient tissue for advanced studies into molecular markers and genetic studies necessary to guide treatment decisions for metastatic NSCLC.
In resectable disease, patients who might have gone straight to surgery in the past now can be considered for neoadjuvant treatments. Here again, says Dr. Feliciano, it is critical for oncologists to understand the biomarkers and molecular profile of the tumor before considering an intervention, and the role of bronchoscopy is key.
A multidisciplinary practice of NSCLC specialists, who have access to on-site or virtual tumor boards, sometimes on an international scale, helps ensure optimal treatment for patients in the increasingly complex NSCLC arena.
--
A. Christine Argento, MD, Associate Professor of Medicine, Department of Pulmonary and Critical Care Medicine, Johns Hopkins University; Director of Bronchoscopy, Department of Interventional Pulmonary Medicine, Johns Hopkins Hospital, Baltimore, Maryland
A. Christine Argento, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Biodesix; Olympus; Cook; Intuitive; Boston Scientific
Josephine L. Feliciano, MD, Associate Professor, Clinical Director, Sidney Kimmel Cancer Center, Johns Hopkins University Hospital, Baltimore, Maryland
Josephine L. Feliciano, MD, has disclosed the following relevant financial relationships:
Received research grant from: Bristol-Myers; Pfizer; AstraZeneca.
Received income in an amount equal to or greater than $250 from: Genentech; AstraZeneca; Eli Lilly; Merck; Regeneron; Coherus; Takeda; Bristol-Myers
Can lung cancer ID be as easy as breathing into an analyzer?
A study published in May in The Lancet journal eClinicalMedicine reports that
The tool was successfully used to identify, in 84 patients, 16 lung cancer–related carcinogenic volatile compounds (VOCs), such as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan – some of which are compounds used in the production of common household goods, such as furniture, carpeting, and wood floors.
“The test is anticipated to be highlighted for primary screening of lung cancer but not the final diagnosis,” according to study authors who were led by Peiyu Wang, MD, PhD, chair of social medicine and health at Peking (China) University.
While early diagnosis and treatment are critical for improving lung cancer survival, early detection of lung cancer is challenging because of the lack of clinical manifestations and specific biomarkers. Annual CT scans are costly and include radiation exposure, Dr. Wang and his associates wrote.
Breathomics testing is considered a promising method for detection and screening for lung cancer. It has been under study for years and in 2014, researchers from Belgium published a review in Cancer Epidemiology Biomarkers and Prevention documenting the use of VOCs as early diagnostic or prognostic biomarkers for mesothelioma.
Lung cancer breath biomarkers identified in various studies have been highly heterogeneous because of differing sample collection methods, varying patient conditions, testing environments, and analysis methods. As a result, there currently is no breathomics test for lung cancer screening, Dr. Wang said in an interview.
In terms of its potential as a lung cancer screening tool, “Clinicians may introduce this test for people with high risk for lung cancer, such as elderly smokers, or people with suspected symptoms. It may also be introduced for young populations with subjective or objective needs to screen for lung cancer. As the proportion of lung adenocarcinoma in nonsmoking young women is increasing, the test may be a good method for lung cancer screening in this population,” Dr. Wang said.
After adjusting for age, sex, smoking, and comorbidities, researchers found elevated levels for 16 VOCs in patients with lung cancer. A diagnostic model including the 16 VOCs achieved an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. A model including the top eight VOCs achieved an area under the curve of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%.
After selecting 28 VOCs as candidates through a literature review, Dr. Wang and associates conducted a prospective discovery study from Sept. 1 to Dec. 31, 2020, using high-pressure photon ionization time-of-flight mass spectrometry to evaluate their performance for lung cancer diagnosis. The validation study included 157 lung cancer patients (mean age 57.0 years; 54.1 percent female) and 368 volunteers (mean age 44.5 years; 31.3% female).
“The external validation confirmed good performance of these biomarkers in lung cancer detection,” the researchers stated. It helped, they added, to solve the heterogeneity among published studies, establishing both 16 VOCs and 8 VOCS for lung cancer screening.
The authors stated that a large gap exists between breathomics research and clinical practices in lung cancer detection and screening. While the validated 16 VOCs, mainly aldehydes and hydrocarbon, showed potential for promoting this lung cancer screening strategy, more scientific studies are warranted to investigate the underlying mechanisms of identified lung cancer VOCs.
Dr. Wang declared no competing interests.
A study published in May in The Lancet journal eClinicalMedicine reports that
The tool was successfully used to identify, in 84 patients, 16 lung cancer–related carcinogenic volatile compounds (VOCs), such as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan – some of which are compounds used in the production of common household goods, such as furniture, carpeting, and wood floors.
“The test is anticipated to be highlighted for primary screening of lung cancer but not the final diagnosis,” according to study authors who were led by Peiyu Wang, MD, PhD, chair of social medicine and health at Peking (China) University.
While early diagnosis and treatment are critical for improving lung cancer survival, early detection of lung cancer is challenging because of the lack of clinical manifestations and specific biomarkers. Annual CT scans are costly and include radiation exposure, Dr. Wang and his associates wrote.
Breathomics testing is considered a promising method for detection and screening for lung cancer. It has been under study for years and in 2014, researchers from Belgium published a review in Cancer Epidemiology Biomarkers and Prevention documenting the use of VOCs as early diagnostic or prognostic biomarkers for mesothelioma.
Lung cancer breath biomarkers identified in various studies have been highly heterogeneous because of differing sample collection methods, varying patient conditions, testing environments, and analysis methods. As a result, there currently is no breathomics test for lung cancer screening, Dr. Wang said in an interview.
In terms of its potential as a lung cancer screening tool, “Clinicians may introduce this test for people with high risk for lung cancer, such as elderly smokers, or people with suspected symptoms. It may also be introduced for young populations with subjective or objective needs to screen for lung cancer. As the proportion of lung adenocarcinoma in nonsmoking young women is increasing, the test may be a good method for lung cancer screening in this population,” Dr. Wang said.
After adjusting for age, sex, smoking, and comorbidities, researchers found elevated levels for 16 VOCs in patients with lung cancer. A diagnostic model including the 16 VOCs achieved an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. A model including the top eight VOCs achieved an area under the curve of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%.
After selecting 28 VOCs as candidates through a literature review, Dr. Wang and associates conducted a prospective discovery study from Sept. 1 to Dec. 31, 2020, using high-pressure photon ionization time-of-flight mass spectrometry to evaluate their performance for lung cancer diagnosis. The validation study included 157 lung cancer patients (mean age 57.0 years; 54.1 percent female) and 368 volunteers (mean age 44.5 years; 31.3% female).
“The external validation confirmed good performance of these biomarkers in lung cancer detection,” the researchers stated. It helped, they added, to solve the heterogeneity among published studies, establishing both 16 VOCs and 8 VOCS for lung cancer screening.
The authors stated that a large gap exists between breathomics research and clinical practices in lung cancer detection and screening. While the validated 16 VOCs, mainly aldehydes and hydrocarbon, showed potential for promoting this lung cancer screening strategy, more scientific studies are warranted to investigate the underlying mechanisms of identified lung cancer VOCs.
Dr. Wang declared no competing interests.
A study published in May in The Lancet journal eClinicalMedicine reports that
The tool was successfully used to identify, in 84 patients, 16 lung cancer–related carcinogenic volatile compounds (VOCs), such as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan – some of which are compounds used in the production of common household goods, such as furniture, carpeting, and wood floors.
“The test is anticipated to be highlighted for primary screening of lung cancer but not the final diagnosis,” according to study authors who were led by Peiyu Wang, MD, PhD, chair of social medicine and health at Peking (China) University.
While early diagnosis and treatment are critical for improving lung cancer survival, early detection of lung cancer is challenging because of the lack of clinical manifestations and specific biomarkers. Annual CT scans are costly and include radiation exposure, Dr. Wang and his associates wrote.
Breathomics testing is considered a promising method for detection and screening for lung cancer. It has been under study for years and in 2014, researchers from Belgium published a review in Cancer Epidemiology Biomarkers and Prevention documenting the use of VOCs as early diagnostic or prognostic biomarkers for mesothelioma.
Lung cancer breath biomarkers identified in various studies have been highly heterogeneous because of differing sample collection methods, varying patient conditions, testing environments, and analysis methods. As a result, there currently is no breathomics test for lung cancer screening, Dr. Wang said in an interview.
In terms of its potential as a lung cancer screening tool, “Clinicians may introduce this test for people with high risk for lung cancer, such as elderly smokers, or people with suspected symptoms. It may also be introduced for young populations with subjective or objective needs to screen for lung cancer. As the proportion of lung adenocarcinoma in nonsmoking young women is increasing, the test may be a good method for lung cancer screening in this population,” Dr. Wang said.
After adjusting for age, sex, smoking, and comorbidities, researchers found elevated levels for 16 VOCs in patients with lung cancer. A diagnostic model including the 16 VOCs achieved an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. A model including the top eight VOCs achieved an area under the curve of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%.
After selecting 28 VOCs as candidates through a literature review, Dr. Wang and associates conducted a prospective discovery study from Sept. 1 to Dec. 31, 2020, using high-pressure photon ionization time-of-flight mass spectrometry to evaluate their performance for lung cancer diagnosis. The validation study included 157 lung cancer patients (mean age 57.0 years; 54.1 percent female) and 368 volunteers (mean age 44.5 years; 31.3% female).
“The external validation confirmed good performance of these biomarkers in lung cancer detection,” the researchers stated. It helped, they added, to solve the heterogeneity among published studies, establishing both 16 VOCs and 8 VOCS for lung cancer screening.
The authors stated that a large gap exists between breathomics research and clinical practices in lung cancer detection and screening. While the validated 16 VOCs, mainly aldehydes and hydrocarbon, showed potential for promoting this lung cancer screening strategy, more scientific studies are warranted to investigate the underlying mechanisms of identified lung cancer VOCs.
Dr. Wang declared no competing interests.
FROM ECLINICAL MEDICINE
Climate change and air pollution seen through the cancer lens
Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.
leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.
The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.
Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.
The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).
A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).
A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.
Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m3) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m3).
What does air pollution have to do with climate change? They both come from the burning of fossil fuels
Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.
The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.
Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.
Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.
leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.
The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.
Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.
The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).
A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).
A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.
Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m3) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m3).
What does air pollution have to do with climate change? They both come from the burning of fossil fuels
Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.
The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.
Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.
Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.
leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.
The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.
Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.
The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).
A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).
A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.
Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m3) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m3).
What does air pollution have to do with climate change? They both come from the burning of fossil fuels
Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.
The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.
Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.
Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Advanced squamous NSCLC: NFE2L2 and KEAP1 mutations tied to worse real-world PFS
Key clinical point: NFE2L2 and KEAP1 mutations account for 31.6% of all advanced squamous cell non-small cell lung cancer (NSCLC) cases, and these mutations are associated with worse real-world progression-free survival (PFS) after first-line therapy.
Major finding: NFE2L2 and KEAP1 mutations were detected in 31.6% of patients. Patients harboring these mutations had a shorter real-world PFS after first-line therapy (4.54 vs 6.25 months with wild-type disease; P = .0027).
Study details: The data come from a retrospective cohort study of 703 patients with advanced squamous cell NSCLC from a real-world US clinicogenomic database.
Disclosures: The study was funded by Takeda Development Center Americas, Inc. Y Wu, Y Yin, V Crossland, S Vincent, N Lineberry, and DV Faller are employees of Takeda Development Center Americas, Inc. PK Paik reported ties with various pharmaceutical companies.
Source: Wu Y et al. Survival outcomes and treatment patterns in patients with NFE2L2 and/or KEAP1 mutation-positive advanced squamous cell NSCLC using a real-world clinico-genomic database. Clin Lung Cancer. 2022 (May 10). Doi: 10.1016/j.cllc.2022.05.008
Key clinical point: NFE2L2 and KEAP1 mutations account for 31.6% of all advanced squamous cell non-small cell lung cancer (NSCLC) cases, and these mutations are associated with worse real-world progression-free survival (PFS) after first-line therapy.
Major finding: NFE2L2 and KEAP1 mutations were detected in 31.6% of patients. Patients harboring these mutations had a shorter real-world PFS after first-line therapy (4.54 vs 6.25 months with wild-type disease; P = .0027).
Study details: The data come from a retrospective cohort study of 703 patients with advanced squamous cell NSCLC from a real-world US clinicogenomic database.
Disclosures: The study was funded by Takeda Development Center Americas, Inc. Y Wu, Y Yin, V Crossland, S Vincent, N Lineberry, and DV Faller are employees of Takeda Development Center Americas, Inc. PK Paik reported ties with various pharmaceutical companies.
Source: Wu Y et al. Survival outcomes and treatment patterns in patients with NFE2L2 and/or KEAP1 mutation-positive advanced squamous cell NSCLC using a real-world clinico-genomic database. Clin Lung Cancer. 2022 (May 10). Doi: 10.1016/j.cllc.2022.05.008
Key clinical point: NFE2L2 and KEAP1 mutations account for 31.6% of all advanced squamous cell non-small cell lung cancer (NSCLC) cases, and these mutations are associated with worse real-world progression-free survival (PFS) after first-line therapy.
Major finding: NFE2L2 and KEAP1 mutations were detected in 31.6% of patients. Patients harboring these mutations had a shorter real-world PFS after first-line therapy (4.54 vs 6.25 months with wild-type disease; P = .0027).
Study details: The data come from a retrospective cohort study of 703 patients with advanced squamous cell NSCLC from a real-world US clinicogenomic database.
Disclosures: The study was funded by Takeda Development Center Americas, Inc. Y Wu, Y Yin, V Crossland, S Vincent, N Lineberry, and DV Faller are employees of Takeda Development Center Americas, Inc. PK Paik reported ties with various pharmaceutical companies.
Source: Wu Y et al. Survival outcomes and treatment patterns in patients with NFE2L2 and/or KEAP1 mutation-positive advanced squamous cell NSCLC using a real-world clinico-genomic database. Clin Lung Cancer. 2022 (May 10). Doi: 10.1016/j.cllc.2022.05.008
Lung cancer: Diagnostic method using breath biomarkers shows promise
Key clinical point: A new breath biomarker-based diagnostic method shows promise by identifying 16 cancer-derived volatile organic compounds (VOC) that have high sensitivity and specificity in patients with lung cancer.
Major finding: In the discovery phase, 16 VOC with peak intensity most altered before vs after surgery were identified. In the validation phase, the 16 VOC-based diagnostic model demonstrated an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1%.
Study details: The discovery phase involved a prospective cohort study of 84 patients with lung cancer who were tested for 28 VOC before and after surgery. The promising VOC were further assessed in the validation phase which included 157 patients with lung cancer and 368 healthy controls.
Disclosures: The research was funded by the National Natural Science Foundation of China and others. The authors declared no competing interests.
Source: Wang P et al. Identification of lung cancer breath biomarkers based on perioperative breathomics testing: A prospective observational study. EClinicalMedicine. 2022;47:101384 (Apr 26). Doi: 10.1016/j.eclinm.2022.101384
Key clinical point: A new breath biomarker-based diagnostic method shows promise by identifying 16 cancer-derived volatile organic compounds (VOC) that have high sensitivity and specificity in patients with lung cancer.
Major finding: In the discovery phase, 16 VOC with peak intensity most altered before vs after surgery were identified. In the validation phase, the 16 VOC-based diagnostic model demonstrated an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1%.
Study details: The discovery phase involved a prospective cohort study of 84 patients with lung cancer who were tested for 28 VOC before and after surgery. The promising VOC were further assessed in the validation phase which included 157 patients with lung cancer and 368 healthy controls.
Disclosures: The research was funded by the National Natural Science Foundation of China and others. The authors declared no competing interests.
Source: Wang P et al. Identification of lung cancer breath biomarkers based on perioperative breathomics testing: A prospective observational study. EClinicalMedicine. 2022;47:101384 (Apr 26). Doi: 10.1016/j.eclinm.2022.101384
Key clinical point: A new breath biomarker-based diagnostic method shows promise by identifying 16 cancer-derived volatile organic compounds (VOC) that have high sensitivity and specificity in patients with lung cancer.
Major finding: In the discovery phase, 16 VOC with peak intensity most altered before vs after surgery were identified. In the validation phase, the 16 VOC-based diagnostic model demonstrated an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1%.
Study details: The discovery phase involved a prospective cohort study of 84 patients with lung cancer who were tested for 28 VOC before and after surgery. The promising VOC were further assessed in the validation phase which included 157 patients with lung cancer and 368 healthy controls.
Disclosures: The research was funded by the National Natural Science Foundation of China and others. The authors declared no competing interests.
Source: Wang P et al. Identification of lung cancer breath biomarkers based on perioperative breathomics testing: A prospective observational study. EClinicalMedicine. 2022;47:101384 (Apr 26). Doi: 10.1016/j.eclinm.2022.101384
Lung cancer: Noncancerous chest CT features may boost survival prediction
Key clinical point: In patients with stage I lung cancer treated with stereotactic body radiation therapy (SBRT), a model incorporating noncancerous imaging features on chest computed tomography (CT) and clinical features vs clinical features alone performed better at predicting overall survival (OS).
Major finding: The model that incorporated both clinical and imaging features vs the model that incorporated only clinical features performed better at predicting 5-year OS (area under the curve 0.75 vs 0.61; P < .01). Independent risk factors for shorter OS were elevated coronary artery calcium score, increased pulmonary artery-to-aorta ratio, and decreased thoracic skeletal muscle index.
Study details: The data come from a retrospective study involving 282 patients with stage I lung cancer treated with SBRT. Several clinical markers were assessed from pretreatment chest CT images.
Disclosures: No funding information was available. The corresponding author FJ Fintelmann reported no relevant financial relationships.
Source: Tahir I et al. Utility of noncancerous chest CT features for predicting overall survival and noncancer death in patients with stage I lung cancer treated with stereotactic body radiotherapy. AJR Am J Roentgenol. 2022 (Apr 13). Doi: 10.2214/AJR.22.27484
Key clinical point: In patients with stage I lung cancer treated with stereotactic body radiation therapy (SBRT), a model incorporating noncancerous imaging features on chest computed tomography (CT) and clinical features vs clinical features alone performed better at predicting overall survival (OS).
Major finding: The model that incorporated both clinical and imaging features vs the model that incorporated only clinical features performed better at predicting 5-year OS (area under the curve 0.75 vs 0.61; P < .01). Independent risk factors for shorter OS were elevated coronary artery calcium score, increased pulmonary artery-to-aorta ratio, and decreased thoracic skeletal muscle index.
Study details: The data come from a retrospective study involving 282 patients with stage I lung cancer treated with SBRT. Several clinical markers were assessed from pretreatment chest CT images.
Disclosures: No funding information was available. The corresponding author FJ Fintelmann reported no relevant financial relationships.
Source: Tahir I et al. Utility of noncancerous chest CT features for predicting overall survival and noncancer death in patients with stage I lung cancer treated with stereotactic body radiotherapy. AJR Am J Roentgenol. 2022 (Apr 13). Doi: 10.2214/AJR.22.27484
Key clinical point: In patients with stage I lung cancer treated with stereotactic body radiation therapy (SBRT), a model incorporating noncancerous imaging features on chest computed tomography (CT) and clinical features vs clinical features alone performed better at predicting overall survival (OS).
Major finding: The model that incorporated both clinical and imaging features vs the model that incorporated only clinical features performed better at predicting 5-year OS (area under the curve 0.75 vs 0.61; P < .01). Independent risk factors for shorter OS were elevated coronary artery calcium score, increased pulmonary artery-to-aorta ratio, and decreased thoracic skeletal muscle index.
Study details: The data come from a retrospective study involving 282 patients with stage I lung cancer treated with SBRT. Several clinical markers were assessed from pretreatment chest CT images.
Disclosures: No funding information was available. The corresponding author FJ Fintelmann reported no relevant financial relationships.
Source: Tahir I et al. Utility of noncancerous chest CT features for predicting overall survival and noncancer death in patients with stage I lung cancer treated with stereotactic body radiotherapy. AJR Am J Roentgenol. 2022 (Apr 13). Doi: 10.2214/AJR.22.27484
Extensive-stage SCLC: Anlotinib plus platinum-etoposide shows promise
Key clinical point: Frontline therapy with anlotinib plus platinum-etoposide chemotherapy shows favorable outcomes in patients with extensive-stage (ES) small-cell lung cancer (SCLC).
Major finding: The median progression-free survival was 8.02 (95% CI 6.90-9.66) months and the overall survival was 15.87 (95% CI 10.38-18.89) months. The objective response rate was 85.71% (95% CI 69.74%-95.19%) and the disease control rate was 94.29% (95% CI 80.84%-99.30%). The incidence of grade 3-4 adverse events was 40%.
Study details: The data come from a phase 2 single-arm trial of anlotinib plus platinum-etoposide in 35 patients with ES-SCLC at a single center in China.
Disclosures: The trial was funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. The authors declared no competing interests.
Source: Deng P et al. Anlotinib plus platinum-etoposide as a first-line treatment for extensive-stage small cell lung cancer: A single-arm trial. Cancer Med. 2022 (May 8). Doi: 10.1002/cam4.4736
Key clinical point: Frontline therapy with anlotinib plus platinum-etoposide chemotherapy shows favorable outcomes in patients with extensive-stage (ES) small-cell lung cancer (SCLC).
Major finding: The median progression-free survival was 8.02 (95% CI 6.90-9.66) months and the overall survival was 15.87 (95% CI 10.38-18.89) months. The objective response rate was 85.71% (95% CI 69.74%-95.19%) and the disease control rate was 94.29% (95% CI 80.84%-99.30%). The incidence of grade 3-4 adverse events was 40%.
Study details: The data come from a phase 2 single-arm trial of anlotinib plus platinum-etoposide in 35 patients with ES-SCLC at a single center in China.
Disclosures: The trial was funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. The authors declared no competing interests.
Source: Deng P et al. Anlotinib plus platinum-etoposide as a first-line treatment for extensive-stage small cell lung cancer: A single-arm trial. Cancer Med. 2022 (May 8). Doi: 10.1002/cam4.4736
Key clinical point: Frontline therapy with anlotinib plus platinum-etoposide chemotherapy shows favorable outcomes in patients with extensive-stage (ES) small-cell lung cancer (SCLC).
Major finding: The median progression-free survival was 8.02 (95% CI 6.90-9.66) months and the overall survival was 15.87 (95% CI 10.38-18.89) months. The objective response rate was 85.71% (95% CI 69.74%-95.19%) and the disease control rate was 94.29% (95% CI 80.84%-99.30%). The incidence of grade 3-4 adverse events was 40%.
Study details: The data come from a phase 2 single-arm trial of anlotinib plus platinum-etoposide in 35 patients with ES-SCLC at a single center in China.
Disclosures: The trial was funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. The authors declared no competing interests.
Source: Deng P et al. Anlotinib plus platinum-etoposide as a first-line treatment for extensive-stage small cell lung cancer: A single-arm trial. Cancer Med. 2022 (May 8). Doi: 10.1002/cam4.4736