Entrectinib in Asian patients with ROS1 fusion-positive non-small cell lung cancer: updated efficacy and safety analysis.

[BACKGROUND] In an integrated analysis of phase I/II trials (STARTRK-2, STARTRK-1, ALKA-372-001), entrectinib induced responses in global populations with advanced ROS1-fusion positive (ROS1-fp) non-small cell lung cancer (NSCLC). This study reports updated efficacy and safety data in Asian patients from the integrated analysis (cutoff: 16 July 2023).

[METHODS] Asian patients with ROS1 tyrosine kinase inhibitor-naïve locally advanced/metastatic ROS1-fp NSCLC, with/without central nervous system (CNS) metastasis were included. The primary endpoints were overall response rate (ORR) and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, IC-DoR, and safety. An exploratory subgroup analysis of patients naïve to systemic therapy in the metastatic setting (1L) was also investigated.

[RESULTS] The efficacy-evaluable population included 99 patients. Median (range) age was 53 (20, 86) years; 32.3 % of patients had baseline CNS metastases. Confirmed ORR was 68.7 % (95 % confidence interval [CI] 58.6 %-77.6 %); median DoR was 18.6 months (95 % CI 11.1-38.5). Confirmed IC-ORR was 34.8 % (95 % CI 16.4 %-57.3 %); median IC-DoR was 9.4 months (95 % CI 6.8-not evaluable). Median time to CNS progression was 28.9 months (95 % CI 15.7-41.4). In the 1L population (n = 40), confirmed ORR was 67.5 % (95 % CI 50.9 %-81.4 %); median DoR was 38.5 months (95 % CI 11.1-not evaluable). The most frequent treatment-related adverse events were weight increased (45.9 %), constipation (40.4 %), and dysgeusia (39.4 %).

[CONCLUSION] This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.