TY - JOUR
T1 - Association between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non-Small Cell Lung Cancer
AU - Popat, Sanjay
AU - Liu, Stephen V.
AU - Scheuer, Nicolas
AU - Gupta, Alind
AU - Hsu, Grace G.
AU - Ramagopalan, Sreeram V.
AU - Griesinger, Frank
AU - Subbiah, Vivek
N1 - Funding Information:
Administrative, technical, or material support: Popat, Hsu, Ramagopalan, Subbiah. Supervision: Popat, Liu, Hsu, Ramagopalan, Griesinger, Subbiah. Conflict of Interest Disclosures: Dr Popat reported receiving personal fees from Amgen Consultancy, AstraZeneca, Bayer, BeiGene, Blueprint, Bristol Meyers Squibb, Boehringer Ingelheim, Daiichi Sankyo, GSK, Guardant Health, Incyte, Janssen, Eli Lilly, Merck Serono, Merck, Novartis, Roche, Takeda, Pfizer, Seattle Genetics, and Turning Point Therapeutics outside the submitted work. Dr Liu reported receiving grants from Alkermes, Bayer, Blueprint Medicines, Bristol Myers Squibb, Elevation Oncology, Eli Lilly, Genentech, Gileady, Merck, Merus, Pfizer, Rain Therapeutics, RAPT Therapeutics, Nuvalent, Turning Point Therapeutics and personal fees from Amgen, AstraZeneca, Bayer, Beigene, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech, Gilead, Guardant Medicines, Janssen, Jazz Pharmaceuticals, Eli Lilly, Merck, Novartis, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics outside the submitted work. Dr Scheuer reported receiving personal fees from Roche during the conduct of the study and receiving employee shares from Roche and Novartis outside the submitted work. Dr Gupta reported receiving support Roche during the conduct of the study. Dr Hsu reported receiving grants from Roche during the conduct of the study. Dr Ramagopalan reported receiving personal fees from Roche during the conduct of the study. Dr Griesinger reported receiving grants and personal fees from Merck during the conduct of the study and receiving grants and personal fees from Amgen, Astra Zeneca, Merck, Roche, Bristol Meyers Squibb, Pfizer, Boehringer Ingelheim, GSK, Siemens, Eli Lilly, Novartis, and Takeda outside the submitted work. Dr Subbiah reported receiving grants from Eli Lilly, Blueprint Medicines Corporation, Turning Point Therapeutics, Boston Pharmaceuticals and Helsinn Pharmaceuticals serving on an advisory board with Eli Lilly during the conduct of the study. Dr Subbiah also reported receiving grants from Roche/Genentech, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Altum, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, National Cancer Institute Cancer Therapy Evaluation Program, University of Texas MD Anderson Cancer Center, Turning Point Therapeutics, Boston Pharmaceuticals, Novartis, Pharmamar, Medimmune and serving as a consultant for Helsinn, Incyte, QED Pharma, Daiichi-Sankyo, Signant Health, Novartis, Relay therapeutics, Roche, Medimmune and receiving support from Pharmamar, Incyte, ASCO, ESMO, and Medscape outside the submitted work.
Publisher Copyright:
© 2021 IOS Press. All rights reserved.
PY - 2022/5/25
Y1 - 2022/5/25
N2 - Importance: There is a need to tailor treatments to patients who are most likely to derive the greatest benefit from them to improve patient outcomes and enhance cost-effectiveness of cancer therapies. Objective: To compare overall survival (OS) between patients with a current or former history of smoking with patients who never smoked and initiated pembrolizumab monotherapy as first-line (1L) treatment for advanced non-small lung cancer (NSCLC). Design, Setting, and Participants: This retrospective cohort study compared patients diagnosed with advanced NSCLC aged 18 or higher selected from a nationwide real-world database originating from more than 280 US cancer clinics. The study inclusion period was from January 1, 2011, to October 1, 2019. Exposures: Smoking status at the time of NSCLC diagnosis. Main Outcomes and Measures: OS measured from initiation of 1L pembrolizumab monotherapy. Results: In this retrospective cohort study, a total of 1166 patients (median [IQR] age, 72.9 [15.3] years; 581 [49.8%] men and 585 [50.2%] women) were assessed in the primary analysis, including 91 patients [7.8%] with no history of smoking (ie, never-smokers) and 1075 patients [92.2%] who currently or formerly smoked (ie, ever-smokers). Compared with ever-smokers, never-smokers were older (median age [IQR] of 78.2 [12.0] vs 72.7 [15.5] years), more likely to be female (61 [67.0%] vs 524 [48.7%]) and to have been diagnosed with nonsquamous tumor histology (70 [76.9%] vs 738 [68.7%]). After adjustment for baseline covariates, ever-smokers who initiated 1L pembrolizumab had significantly prolonged OS compared to never-smokers (median OS: 12.8 [10.9-14.6] vs 6.5 [3.3-13.8] months; hazard ratio (HR): 0.69 [95% CI, 0.50-0.95]). This trend was observed across all sensitivity analyses for the 1L pembrolizumab cohort, but not for initiators of 1L platinum chemotherapy, for which ever-smokers showed significantly shorter OS compared with never-smokers (HR, 1.2 [95% CI, 1.07-1.33]). Conclusions and Relevance: In patients with advanced NSCLC who received 1L pembrolizumab monotherapy in routine clinical practices in the US, patients who reported a current or former history of smoking at the time of diagnosis had consistently longer OS than never-smokers. This finding suggests that in never-smoking advanced NSCLC, 1L pembrolizumab monotherapy may not be the optimal therapy selection, and genomic testing for potential genomically matched therapies should be prioritized over pembrolizumab in never-smokers..
AB - Importance: There is a need to tailor treatments to patients who are most likely to derive the greatest benefit from them to improve patient outcomes and enhance cost-effectiveness of cancer therapies. Objective: To compare overall survival (OS) between patients with a current or former history of smoking with patients who never smoked and initiated pembrolizumab monotherapy as first-line (1L) treatment for advanced non-small lung cancer (NSCLC). Design, Setting, and Participants: This retrospective cohort study compared patients diagnosed with advanced NSCLC aged 18 or higher selected from a nationwide real-world database originating from more than 280 US cancer clinics. The study inclusion period was from January 1, 2011, to October 1, 2019. Exposures: Smoking status at the time of NSCLC diagnosis. Main Outcomes and Measures: OS measured from initiation of 1L pembrolizumab monotherapy. Results: In this retrospective cohort study, a total of 1166 patients (median [IQR] age, 72.9 [15.3] years; 581 [49.8%] men and 585 [50.2%] women) were assessed in the primary analysis, including 91 patients [7.8%] with no history of smoking (ie, never-smokers) and 1075 patients [92.2%] who currently or formerly smoked (ie, ever-smokers). Compared with ever-smokers, never-smokers were older (median age [IQR] of 78.2 [12.0] vs 72.7 [15.5] years), more likely to be female (61 [67.0%] vs 524 [48.7%]) and to have been diagnosed with nonsquamous tumor histology (70 [76.9%] vs 738 [68.7%]). After adjustment for baseline covariates, ever-smokers who initiated 1L pembrolizumab had significantly prolonged OS compared to never-smokers (median OS: 12.8 [10.9-14.6] vs 6.5 [3.3-13.8] months; hazard ratio (HR): 0.69 [95% CI, 0.50-0.95]). This trend was observed across all sensitivity analyses for the 1L pembrolizumab cohort, but not for initiators of 1L platinum chemotherapy, for which ever-smokers showed significantly shorter OS compared with never-smokers (HR, 1.2 [95% CI, 1.07-1.33]). Conclusions and Relevance: In patients with advanced NSCLC who received 1L pembrolizumab monotherapy in routine clinical practices in the US, patients who reported a current or former history of smoking at the time of diagnosis had consistently longer OS than never-smokers. This finding suggests that in never-smoking advanced NSCLC, 1L pembrolizumab monotherapy may not be the optimal therapy selection, and genomic testing for potential genomically matched therapies should be prioritized over pembrolizumab in never-smokers..
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U2 - 10.1001/jamanetworkopen.2022.14046
DO - 10.1001/jamanetworkopen.2022.14046
M3 - Article
C2 - 35612853
AN - SCOPUS:85131106327
SN - 2574-3805
VL - 5
SP - E2214046
JO - JAMA Network Open
JF - JAMA Network Open
IS - 5
ER -