3rd-line anaplastic lymphoma kinase (ALK) inhibitors (ALKi) in advanced non-small cell lung cancer (aNSCLC): Real-world comparison to non-ALKi therapy.

Abstract

e21685 Background: ALKi represent the standard 1st- and 2nd -line treatment (Tx) for ALK+ aNSCLC patients (pts). The value of ALKi in the 3rd-line setting is unclear. We retrospectively assessed the real-world impact of a 3rd -line ALKi vs. non-ALKi Tx in ALK+ aNSCLC pts. Methods: Consecutive ALK+ aNSCLC pts were identified in the working databases of 7 Israeli oncology centers; pts receiving any systemic Tx beyond 2 different ALKi were selected for the comparative analysis. Pts whose immediate next Tx line (post-2nd-ALKi) was a 3rdALKi (Group (Gr) A) were compared to pts whose immediate next Tx line (post-2nd-ALKi) was non-ALKi Tx (Gr B), in terms of overall survival (OS) and time to next Tx line (TNT). Results: 158 consecutive ALK+ aNSCLC pts diagnosed in January 2011 - March 2019 were included, median follow up from diagnosis of aNSCLC was 41 months (mo) (IQR 8-45). Median OS from aNSCLC diagnosis was 56 mo (95% CI 36-66). Post-2nd-ALKi line was a 3rd ALKi for 23 pts (Gr A) and a non-ALKi Tx for 10 pts (Gr B). 7 of Gr B (70%) received ALKi as a later line Tx. Median OS after initiation of post-2nd-ALKi Tx was 27 mo (95% CI, 7-NA) for Gr A vs. 16 mo (95% CI, 7-NA) for Gr B; p-non-significant (NS) with or without adjustment for sex, age, brain metastases. TNT on post-2nd-ALKi Tx was 6 mo (95% CI, 2-27) for Gr A vs. 2.5 mo (95% CI, 0-NA) for Gr B; p-NS. Conclusions: Following progression on a 2ndALKi, OS and TNT were numerically higher for pts receiving a 3rd ALKi, but statistically NS. Extensive exposure of pts in the non-ALKi Tx Gr to an ALKi at a later stage might have impacted these results. Further studies are required to identify patients likely to benefit from ALKi after progressing on 2 or more ALKi Tx lines. [Table: see text]