Efficacy of first‐line immune checkpoint inhibitors in patients with advanced NSCLC with KRAS, MET, FGFR, RET, BRAF, and HER2 alterations

Abstract

Abstract Background In patients with non‐small cell lung cancer (NSCLC) harboring driver alterations, the efficacy of immune checkpoint inhibitors (ICIs) remains uncertain. Our study aimed to examine the first‐line ICI efficacy in patients with NSCLC harboring KRAS, MET, FGFR, RET, BRAF, and HER2 alterations in a real‐world setting. Methods This single‐center, retrospective cohort study included patients with advanced NSCLC harboring KRAS, MET, FGFR, RET, BRAF, HER2 alterations or driver‐negative, and were treated with first‐line ICI therapy. Best overall response, progression‐free survival (PFS), and overall survival (OS) were evaluated. Results Seventy‐eight patients with NSCLC were included (median age, 72 years): 67% were men, 15% were never‐smokers, and 83% had adenocarcinoma. The driver alterations involved KRAS (n = 21), MET (n = 6), FGFR (n = 3), RET (n = 2), BRAF (n = 2), HER2 (n = 1), and driver‐negative (n = 43). The partial responses for KRAS, MET, FGFR, RET, BRAF, HER2, and driver‐negative were 57%, 50%, 100%, 50%, 100%, 0%, and 47%, respectively. The median PFS (months) was 16.2 (95% confidence interval [CI]: 6.3– not reached [NR]) for KRAS, 2.8 (95% CI: 2.7–NR) for MET, 11.7 (95% CI: 5.9–NR) for other alterations (FGFR, RET, BRAF, and HER2), and 10.0 (95% CI: 3.7–14.3) for driver‐negative, respectively. The median OS (months) was 31.3 (95% CI: 9.0–NR) for KRAS, not reached for MET, 23.5 (95% CI: 18.3–NR) for other alterations, and 21.1 (95% CI: 15.2–NR) for driver‐negative, respectively. Conclusions The benefit of the first‐line ICI was similar in advanced NSCLC regardless of the driver alterations, except for MET alterations.

Keywords

• immunotherapy
• KRAS mutation
• lung cancer
• MET mutation
• oncogenic drivers