Smoking impacts benefit of first-line pembrolizumab in lung cancer

In a retrospective study, Dr. Vivek Subbiah of MD Anderson Cancer Center in Houston and colleagues found that patients without a history of smoking may not derive the same overall survival benefit from first-line pembrolizumab as current or former smokers.

Their findings are in line with pooled data from two randomized clinical trials that found significantly higher efficacy of pembrolizumab and another PD-1 inhibitor (nivolumab) relative to chemotherapy in current or former smokers compared with never smokers.

Dr. Subbiah and colleagues analyzed data on 1,166 patients with advanced NSCLC who received first-line pembrolizumab monotherapy; 91 (8%) had no history of smoking and 1,075 (92%) were current or former smokers.

Compared with ever-smokers, never-smokers were older, more likely to be female and to have nonsquamous tumor histology.

After adjusting for baseline variables, ever-smokers who initiated first-line pembrolizumab had significantly prolonged overall survival compared with never-smokers (median OS, 12.8 vs. 6.5 months; hazard ratio, 0.69).

This trend was observed across all sensitivity analyses for the first-line pembrolizumab cohort, but not for initiators of first-line platinum chemotherapy, for which ever-smokers showed significantly shorter overall survival compared with never-smokers (HR, 1.2).

The findings, say the authors, suggest in that patients with advanced NSCLC who have never smoked, 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."

The study had no specific funding. Several authors disclosed relationships with pharmaceutical companies.