Efficacy of immune-checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients harboring activating molecular alterations (ImmunoTarget).

Abstract

9010 Background: Data on ICI activity in patients with oncogenic driver are limited. The aim of this study was to collect further data across various molecular subgroups. Methods: We conducted a retrospective multicenter study of patients receiving ICI for stage IV NSCLC with genomic alterations. Anonymized data were evaluated for clinicopathologic characteristics and outcomes: best response (RECIST v1.1), progression-free survival (PFS) and overall survival (OS) from ICI initiation. Results: We included 527 patients treated in 25 centers The. Molecular alterations involved KRAS (n = 252), EGFR (n = 110), BRAF (n = 38), MET (n = 36), HER2 (n = 23), ALK (n = 18), RET (n = 14), ROS1 (n = 5), and multiple drivers (n = 31). Median age was 60 years, sex-ratio was 1:1, never/former/current smokers were 27/51/22%, and the majority of tumors were adenocarcinoma. ICIs were mainly anti-PD1 (92%) given in the first (5%), second (42%), third (26%), or later line (27%) settings. The best response rate was 19% [15-22%]. The median PFS and OS were 2.8 [2.5-3.1] and 13.3 [9.8-14.8] months, respectively. Outcomes by molecular subtypes are reported below (table 1). EGFR-mutant had shorter PFS compared to KRAS-mutant (p < 0.001). T790M mutation was associated with a shorter PFS than other EGFR mutations (p = 0.0001) whereas the benefit was the same across all KRAS mutation subtypes. Among MET alterations, exon 14 mutations were the most sensitive to ICI. PFS was positively influenced by smoking (p = 0.003) and PDL1 expression (p = 0.02) in the overall population but not for EGFR-mutant. Conclusions: ICI has inconstant efficacy in NSCLC harboring activating mutation. KRAS, BRAF and MET-exon 14 patients derive a greater benefit than EGFR, ALK and RET patients. Driver n Best response (%) PFS OS CR/PR SD PD Median (months*) 6 m PFS (%) 1 y PFS (%) Median (months*) BRAF 38 28.1 28.1 43.8 3.0 35 19 13.6 KRAS 252 27.2 23.1 49.8 3.2 39 26 13.5 ROS1 5 20 0 80 NA NA NA NA MET 36 15.6 34.4 50.0 3.4 33 23 18.4 EGFR 110 11.0 18.0 71.0 2.0 16 6 8.8 HER2 23 9.5 28.6 61.9 3.5 34 17 10.0 RET 14 7.1 21.4 71.4 2.2 16 8 6.5 ALK 18 0 21.4 78.6 2.1 16 8 17.0 *: from ICI initiation. CR/PR : Complete/Partial response, SD/PD Stable/Progressive disease.