Lung Cancer

Combination metformin and epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) therapy improved progression-free survival in patients with EGFR-mutated lung adenocarcinoma, according to results from a phase 2 trial.

“This is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS [progression-free survival],” wrote Oscar Arrieta, MD, of the Instituto Nacional de Cancerología, Mexico, and colleagues in JAMA Oncology.

The open-label, randomized study included 139 patients, 69 of whom were randomly assigned to receive metformin plus EGFR-TKI therapy and 70 of whom received EGFR-TKI monotherapy.

EGFR-TKI therapy was selected based on physician choice and consisted of either afatinib dimaleate, gefitinib, or erlotinib hydrochloride at regular doses. Study patients in the combination arm received metformin 500 mg twice daily.

The primary endpoint was PFS (intent-to-treat population). Secondary endpoints included overall survival (OS), objective response rate, and safety.

After analysis, the researchers found that the median PFS was 13.1 months with metformin-EGFR-TKI combination therapy and 9.9 months with EGFR-TKI monotherapy (hazard ratio, 0.60; P = .03).

In addition, the median OS was also significantly prolonged for patients receiving combined treatment (31.7 months vs. 17.5 months; P = .02).

“Multivariable analysis showed that treatment with metformin is independently associated with longer PFS and OS,” the researchers wrote.

With respect to safety, no significant rise in adverse events was observed, and toxicities were comparable across both treatment groups.

The researchers acknowledged that a key limitation of the study was the absence of a double-blinded design. As a result, various biases could have influenced the results.

“The results from this phase 2 study warrant the design of a larger, phase 3, placebo-controlled study to draw more robust conclusions,” they said.

The study was funded by the National Council for Science and Technology in Mexico. The authors reported financial affiliations with AbbVie, AstraZeneca, Boehringer Ingelheim, Lilly, Bristol-Myers Squibb, Merck, Pfizer, Roche, and several others.

SOURCE: Arrieta O et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.2553.

Combination metformin and epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) therapy improved progression-free survival in patients with EGFR-mutated lung adenocarcinoma, according to results from a phase 2 trial.

“This is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS [progression-free survival],” wrote Oscar Arrieta, MD, of the Instituto Nacional de Cancerología, Mexico, and colleagues in JAMA Oncology.

The open-label, randomized study included 139 patients, 69 of whom were randomly assigned to receive metformin plus EGFR-TKI therapy and 70 of whom received EGFR-TKI monotherapy.

EGFR-TKI therapy was selected based on physician choice and consisted of either afatinib dimaleate, gefitinib, or erlotinib hydrochloride at regular doses. Study patients in the combination arm received metformin 500 mg twice daily.

The primary endpoint was PFS (intent-to-treat population). Secondary endpoints included overall survival (OS), objective response rate, and safety.

After analysis, the researchers found that the median PFS was 13.1 months with metformin-EGFR-TKI combination therapy and 9.9 months with EGFR-TKI monotherapy (hazard ratio, 0.60; P = .03).

In addition, the median OS was also significantly prolonged for patients receiving combined treatment (31.7 months vs. 17.5 months; P = .02).

“Multivariable analysis showed that treatment with metformin is independently associated with longer PFS and OS,” the researchers wrote.

With respect to safety, no significant rise in adverse events was observed, and toxicities were comparable across both treatment groups.

The researchers acknowledged that a key limitation of the study was the absence of a double-blinded design. As a result, various biases could have influenced the results.

“The results from this phase 2 study warrant the design of a larger, phase 3, placebo-controlled study to draw more robust conclusions,” they said.

The study was funded by the National Council for Science and Technology in Mexico. The authors reported financial affiliations with AbbVie, AstraZeneca, Boehringer Ingelheim, Lilly, Bristol-Myers Squibb, Merck, Pfizer, Roche, and several others.

SOURCE: Arrieta O et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.2553.

Combination metformin and epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) therapy improved progression-free survival in patients with EGFR-mutated lung adenocarcinoma, according to results from a phase 2 trial.

“This is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS [progression-free survival],” wrote Oscar Arrieta, MD, of the Instituto Nacional de Cancerología, Mexico, and colleagues in JAMA Oncology.

The open-label, randomized study included 139 patients, 69 of whom were randomly assigned to receive metformin plus EGFR-TKI therapy and 70 of whom received EGFR-TKI monotherapy.

EGFR-TKI therapy was selected based on physician choice and consisted of either afatinib dimaleate, gefitinib, or erlotinib hydrochloride at regular doses. Study patients in the combination arm received metformin 500 mg twice daily.

The primary endpoint was PFS (intent-to-treat population). Secondary endpoints included overall survival (OS), objective response rate, and safety.

After analysis, the researchers found that the median PFS was 13.1 months with metformin-EGFR-TKI combination therapy and 9.9 months with EGFR-TKI monotherapy (hazard ratio, 0.60; P = .03).

In addition, the median OS was also significantly prolonged for patients receiving combined treatment (31.7 months vs. 17.5 months; P = .02).

“Multivariable analysis showed that treatment with metformin is independently associated with longer PFS and OS,” the researchers wrote.

With respect to safety, no significant rise in adverse events was observed, and toxicities were comparable across both treatment groups.

The researchers acknowledged that a key limitation of the study was the absence of a double-blinded design. As a result, various biases could have influenced the results.

“The results from this phase 2 study warrant the design of a larger, phase 3, placebo-controlled study to draw more robust conclusions,” they said.

The study was funded by the National Council for Science and Technology in Mexico. The authors reported financial affiliations with AbbVie, AstraZeneca, Boehringer Ingelheim, Lilly, Bristol-Myers Squibb, Merck, Pfizer, Roche, and several others.

SOURCE: Arrieta O et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.2553.

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Mutations in the tumor suppressor KEAP1 or STK11 genes in patients with metastatic non–small cell lung cancer (mNSCLC) in the randomized, phase 3 MYSTIC trial experienced poorer outcomes than did patients without the mutations, according to an exploratory analysis of trial data.

Sharon Worcester/MDedge News

Mutations in ARID1a, however, were associated with improved overall survival (OS) among patients in the trial who were treated with durvalumab + tremelimumab.

Profiling of circulating tumor DNA from 943 evaluable baseline plasma specimens showed median OS of 7.4 vs. 12.9 months among 170 patients with KEAP1 mutations (m) vs. in 773 with KEAP1 wild type (hazard ratio, 1.64), and 6.8 vs. 12.6 months in patients with STK11m vs. 796 with STK11wt (HR, 1.52), Naiyer A. Rizvi, MD, the Price Family Professor of Medicine, director of Thoracic Oncology, and codirector of Cancer Immunotherapy at Columbia University Irving Medical Center, New York, reported at the World Conference on Lung Cancer.

Objective response rates (ORR) in the groups, respectively, were 17.6% vs. 27.7% for KEAP1m vs. KEAP1wt, and 16.3% vs. 27.6% for STK11m vs. STK11wt, Dr. Rizvi said at the conference, sponsored by the International Association for the Study of Lung Cancer.

This was regardless of MYSTIC trial treatment arm; the open-label, multicenter, global trial compared durvalumab monotherapy or durvalumab plus tremelimumab with platinum-based chemotherapy for the first-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic NSCLC.

Mutations in the ARID1a gene, however, had no impact on OS (12.6 vs. 11.4 months in 114 vs. 829 patients with ARID1am vs. ARID1awt; HR, 0.94), and ORRs, respectively, were 35.1% vs. 24.6%.

When comparing outcomes by treatment arm, the ORRs with chemotherapy were 15.1% vs. 34% for KEAP1m vs. KEAP1wt, 12.2% vs. 33.6% for STK11m vs. STK1wt, and 28.1% vs. 31% for ARID1am vs. ARID1awt.

The ORRs in the durvalumab arm were 16.7% vs. 25.2% for KEAP1m vs. KEAP1st, 14.5% vs. 25.7% for STK11m vs. STK11wt and 25.6% vs. 23.4%, respectively, and in the durvalumab + tremelimumab arm they were 20.6% vs. 23.9% for KEAP1m vs. KEAP1wt, 21.6% vs. 23.6% for STK11m vs. STK11wt.

“The key finding here is really the ARID1a response,” Dr. Rizvi said, noting the “pretty impressive response rates” of 51.3% with ARID1am vs. 19.4% for ARID1awt.

The relationship between gene alterations and response to anti-programmed death-1 (PD-1) therapy with and without anti-CTLA-4 therapy is not well characterized. These findings, which suggest that KEAP1 and STK11 mutations are prognostic for OS in mNSCLC, and that ARID1am may be predictive of OS benefit in patients receiving durvalumab + tremelimumab, provide insights to the potential impact of specific mutations on response to immunotherapy, Dr. Rizvi said.

“STK11 and KEAP1 mutations ... are relatively common mutations – they are actually the third and fourth most common mutations in lung cancer after p53 and KRAS,” he said, adding that they influence outcomes and need to be factored in to analyses of outcomes in lung cancer. “ARID1am patients were about 10% of the population and they did particularly well with durvalumab and tremelimumab, and I think these exploratory analyses can help us think about how we use [tumor mutational burden] and outcomes among cancer patients in future trials.”

The MYSTIC trial was sponsored by AstraZeneca. Dr. Rizvi disclosed royalties related to intellectual property/patents filed by MSKCC and Personal Genome Diagnostics.

SOURCE: Rizvi N et al. WCLC 2019: Abstract OA04.07.

BARCELONA – Mutations in the tumor suppressor KEAP1 or STK11 genes in patients with metastatic non–small cell lung cancer (mNSCLC) in the randomized, phase 3 MYSTIC trial experienced poorer outcomes than did patients without the mutations, according to an exploratory analysis of trial data.

Sharon Worcester/MDedge News

Mutations in ARID1a, however, were associated with improved overall survival (OS) among patients in the trial who were treated with durvalumab + tremelimumab.

Profiling of circulating tumor DNA from 943 evaluable baseline plasma specimens showed median OS of 7.4 vs. 12.9 months among 170 patients with KEAP1 mutations (m) vs. in 773 with KEAP1 wild type (hazard ratio, 1.64), and 6.8 vs. 12.6 months in patients with STK11m vs. 796 with STK11wt (HR, 1.52), Naiyer A. Rizvi, MD, the Price Family Professor of Medicine, director of Thoracic Oncology, and codirector of Cancer Immunotherapy at Columbia University Irving Medical Center, New York, reported at the World Conference on Lung Cancer.

Objective response rates (ORR) in the groups, respectively, were 17.6% vs. 27.7% for KEAP1m vs. KEAP1wt, and 16.3% vs. 27.6% for STK11m vs. STK11wt, Dr. Rizvi said at the conference, sponsored by the International Association for the Study of Lung Cancer.

This was regardless of MYSTIC trial treatment arm; the open-label, multicenter, global trial compared durvalumab monotherapy or durvalumab plus tremelimumab with platinum-based chemotherapy for the first-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic NSCLC.

Mutations in the ARID1a gene, however, had no impact on OS (12.6 vs. 11.4 months in 114 vs. 829 patients with ARID1am vs. ARID1awt; HR, 0.94), and ORRs, respectively, were 35.1% vs. 24.6%.

When comparing outcomes by treatment arm, the ORRs with chemotherapy were 15.1% vs. 34% for KEAP1m vs. KEAP1wt, 12.2% vs. 33.6% for STK11m vs. STK1wt, and 28.1% vs. 31% for ARID1am vs. ARID1awt.

The ORRs in the durvalumab arm were 16.7% vs. 25.2% for KEAP1m vs. KEAP1st, 14.5% vs. 25.7% for STK11m vs. STK11wt and 25.6% vs. 23.4%, respectively, and in the durvalumab + tremelimumab arm they were 20.6% vs. 23.9% for KEAP1m vs. KEAP1wt, 21.6% vs. 23.6% for STK11m vs. STK11wt.

“The key finding here is really the ARID1a response,” Dr. Rizvi said, noting the “pretty impressive response rates” of 51.3% with ARID1am vs. 19.4% for ARID1awt.

The relationship between gene alterations and response to anti-programmed death-1 (PD-1) therapy with and without anti-CTLA-4 therapy is not well characterized. These findings, which suggest that KEAP1 and STK11 mutations are prognostic for OS in mNSCLC, and that ARID1am may be predictive of OS benefit in patients receiving durvalumab + tremelimumab, provide insights to the potential impact of specific mutations on response to immunotherapy, Dr. Rizvi said.

“STK11 and KEAP1 mutations ... are relatively common mutations – they are actually the third and fourth most common mutations in lung cancer after p53 and KRAS,” he said, adding that they influence outcomes and need to be factored in to analyses of outcomes in lung cancer. “ARID1am patients were about 10% of the population and they did particularly well with durvalumab and tremelimumab, and I think these exploratory analyses can help us think about how we use [tumor mutational burden] and outcomes among cancer patients in future trials.”

The MYSTIC trial was sponsored by AstraZeneca. Dr. Rizvi disclosed royalties related to intellectual property/patents filed by MSKCC and Personal Genome Diagnostics.

SOURCE: Rizvi N et al. WCLC 2019: Abstract OA04.07.

BARCELONA – Mutations in the tumor suppressor KEAP1 or STK11 genes in patients with metastatic non–small cell lung cancer (mNSCLC) in the randomized, phase 3 MYSTIC trial experienced poorer outcomes than did patients without the mutations, according to an exploratory analysis of trial data.

Sharon Worcester/MDedge News

Mutations in ARID1a, however, were associated with improved overall survival (OS) among patients in the trial who were treated with durvalumab + tremelimumab.

Profiling of circulating tumor DNA from 943 evaluable baseline plasma specimens showed median OS of 7.4 vs. 12.9 months among 170 patients with KEAP1 mutations (m) vs. in 773 with KEAP1 wild type (hazard ratio, 1.64), and 6.8 vs. 12.6 months in patients with STK11m vs. 796 with STK11wt (HR, 1.52), Naiyer A. Rizvi, MD, the Price Family Professor of Medicine, director of Thoracic Oncology, and codirector of Cancer Immunotherapy at Columbia University Irving Medical Center, New York, reported at the World Conference on Lung Cancer.

Objective response rates (ORR) in the groups, respectively, were 17.6% vs. 27.7% for KEAP1m vs. KEAP1wt, and 16.3% vs. 27.6% for STK11m vs. STK11wt, Dr. Rizvi said at the conference, sponsored by the International Association for the Study of Lung Cancer.

This was regardless of MYSTIC trial treatment arm; the open-label, multicenter, global trial compared durvalumab monotherapy or durvalumab plus tremelimumab with platinum-based chemotherapy for the first-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic NSCLC.

Mutations in the ARID1a gene, however, had no impact on OS (12.6 vs. 11.4 months in 114 vs. 829 patients with ARID1am vs. ARID1awt; HR, 0.94), and ORRs, respectively, were 35.1% vs. 24.6%.

When comparing outcomes by treatment arm, the ORRs with chemotherapy were 15.1% vs. 34% for KEAP1m vs. KEAP1wt, 12.2% vs. 33.6% for STK11m vs. STK1wt, and 28.1% vs. 31% for ARID1am vs. ARID1awt.

The ORRs in the durvalumab arm were 16.7% vs. 25.2% for KEAP1m vs. KEAP1st, 14.5% vs. 25.7% for STK11m vs. STK11wt and 25.6% vs. 23.4%, respectively, and in the durvalumab + tremelimumab arm they were 20.6% vs. 23.9% for KEAP1m vs. KEAP1wt, 21.6% vs. 23.6% for STK11m vs. STK11wt.

“The key finding here is really the ARID1a response,” Dr. Rizvi said, noting the “pretty impressive response rates” of 51.3% with ARID1am vs. 19.4% for ARID1awt.

The relationship between gene alterations and response to anti-programmed death-1 (PD-1) therapy with and without anti-CTLA-4 therapy is not well characterized. These findings, which suggest that KEAP1 and STK11 mutations are prognostic for OS in mNSCLC, and that ARID1am may be predictive of OS benefit in patients receiving durvalumab + tremelimumab, provide insights to the potential impact of specific mutations on response to immunotherapy, Dr. Rizvi said.

“STK11 and KEAP1 mutations ... are relatively common mutations – they are actually the third and fourth most common mutations in lung cancer after p53 and KRAS,” he said, adding that they influence outcomes and need to be factored in to analyses of outcomes in lung cancer. “ARID1am patients were about 10% of the population and they did particularly well with durvalumab and tremelimumab, and I think these exploratory analyses can help us think about how we use [tumor mutational burden] and outcomes among cancer patients in future trials.”

The MYSTIC trial was sponsored by AstraZeneca. Dr. Rizvi disclosed royalties related to intellectual property/patents filed by MSKCC and Personal Genome Diagnostics.

SOURCE: Rizvi N et al. WCLC 2019: Abstract OA04.07.

BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.

Sharon Worcester/ MDedge News

Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.

The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.

Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.

The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.

“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.

The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.

“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.

When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.

“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.

The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.

sworcester@mdedge.com

BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.

Sharon Worcester/ MDedge News

Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.

The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.

Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.

The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.

“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.

The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.

“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.

When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.

“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.

The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.

sworcester@mdedge.com

BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.

Sharon Worcester/ MDedge News

Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.

The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.

Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.

The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.

“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.

The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.

“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.

When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.

“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.

The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.

sworcester@mdedge.com

BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).

Sharon Worcester/ MDedge News

Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.

“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.

Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.

“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.

The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.

In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:

• Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
• Smoking cessation counseling and treatment should be a reimbursable service.
• Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
• Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.

Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.

sworcester@mdedge.com

BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).

Sharon Worcester/ MDedge News

Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.

“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.

Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.

“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.

The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.

In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:

• Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
• Smoking cessation counseling and treatment should be a reimbursable service.
• Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
• Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.

Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.

sworcester@mdedge.com

BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).

Sharon Worcester/ MDedge News

Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.

“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.

Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.

“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.

The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.

In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:

• Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
• Smoking cessation counseling and treatment should be a reimbursable service.
• Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
• Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.

Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.

sworcester@mdedge.com