Format
Scientific article
Publication Date
Published by / Citation
Popat S, Liu SV, Scheuer N, et al. Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non–Small Cell Lung Cancer. JAMA Netw Open. 2022;5(5):e2214046. doi:10.1001/jamanetworkopen.2022.14046
Original Language

English

Keywords
smoking
cancer
Non–Small Cell Lung Cancer
Pembrolizumab

Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non–Small Cell Lung Cancer

Abstract

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.