Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi)

Abstract Objectives Efficacy of immune check-point inhibitors (ICPi) in NSCLC with rare targetable drivers (RTDs) is largely unknown. Materials and Methods Consecutive patients with NSCLC and RTDs (non- EGFR / ALK , n-82) were selected from the Davidoff Cancer Center database. ORR, PFS, OS with ICPi, OS since advanced disease diagnosis, TMB, MSI, and PD-L1 expression were analyzed; uni- and multivariate PFS and OS analyses were done. OS with ICPi was compared between the RTD cohort and the non-selected NSCLC cohort (n-278). Results Of 50 tumors tested, 32%, 38%, and 30% were associated with ≥50%, 1–49% and  0.4), TMB (p > 0.8), or RTD type (p > 0.3). In the multivariate analysis, ECOG PS (p-0.005), targeted agents exposure (p-0.005), and ICPi exposure (p-0.04) were the only variables which correlated with OS since advanced disease diagnosis. Median OS since advanced disease diagnosis comprised 32 months (95% CI, 19.9–44.9) and 13 months (95% CI, 6.6–15.9) for patients who were and were not exposed to ICPi, respectively (log-rank test-6.3; p-0.01). In the inter-cohort comparison, for patients matched for ECOG PS (0/1), median OS with ICPi comprised 17.5 months (95% CI, 8.1-NR) and 8.6 months (95% CI, 6.7-NR) for RTD and non-selected patients, respectively (log-rank test-2.4, p-0.1). Conclusion In NSCLC with RTD, ICPi have favorable efficacy and independent impact on OS. NSCLC with RTD is associated with MSI stable status and variable levels of PD-L1 expression and TMB; their predictive value remains to be determined.