In a retrospective cohort study reported in JAMA Network Open, Sanjay Popat, FRCP, PhD, and colleagues found that among patients initiating first-line pembrolizumab for EGFR and ALK wild-type advanced non–small cell lung cancer (NSCLC), ever-smokers had significantly better overall survival vs never-smokers.
Study Details
The study involved data from the Flatiron Health database, a nationwide longitudinal electronic health record–derived database covering more than 280 U.S. cancer clinics. The study inclusion period was from January 2011 to October 2019.
Key Findings
The study population consisted of 1,166 patients without EGFR or ALK alterations, including 91 never-smokers (7.8%), and 1,075 current or former smokers (ever-smokers; 92.2%). In the entire population, the median age was 72.9 years and 50.2% were women. Compared with ever-smokers, never-smokers were older (median age = 78.2 vs 72.7), were more likely to be women (67% vs 48.7%), and were more likely to have nonsquamous histology (76.9% vs 68.7%).
This finding suggests that in never-smoking [patients with] advanced NSCLC, first-line 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.— Sanjay Popat, FRCP, PhD, and colleagues
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In analysis adjusted for baseline factors, median overall survival after initiation of pembrolizumab was 12.8 months (95% confidence interval [CI] = 10.9–14.6 months) among ever-smokers vs 6.5 months (95% CI = 3.3–13.8 months) among never-smokers (hazard ratio [HR] = 0.69, 95% CI = 0.50–0.95).
In adjusted analysis among 8,375 patients who received first-line platinum-based chemotherapy, including 7,803 ever-smokers (93.2%) and 572 never-smokers (6.8%), never-smokers had significantly improved overall survival (HR = 1.2, 95% CI = 1.06–1.33).
The investigators concluded, “In this retrospective study of patients with EGFR and ALK wild-type advanced NSCLC who received first-line pembrolizumab monotherapy, overall survival was compared between never-smokers and ever-smokers after direct adjustment for differences in prognostic patient characteristics. To our knowledge, this is the first direct comparison suggesting that smoking status is predictive of overall survival after receiving first-line pembrolizumab monotherapy in a large, nationally representative real-world U.S. cohort of patients with advanced NSCLC… This finding suggests that in never-smoking [patients with] advanced NSCLC, first-line 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.”
Vivek Subbiah, MD, of the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center; and Sreeram V. Ramagopalan, PhD, Global Access, F. Hoffmann-La Roche, Basel; are the corresponding authors for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
