Immunotherapy-Treated Non-Small Cell Lung Cancer Patients With Sensitizing Gene Alterations: A Real World Survival Analysis

Mutation-specific tyrosine kinase inhibitors (TKIs) have demonstrated efficacy among patients (pts) with advanced non-small cell lung cancer (aNSCLC) with sensitizing gene alterations (GA). It is unclear how effective immune checkpoint inhibitor (ICI) therapy is among NSCLC pts with sensitizing GA, particularly after TKI failure or resistance. Pts with aNSCLC (stages IIIB/IV at diagnoses, or progression to metastatic disease) diagnosed 01/01/2014-06/01/2020 with sensitizing GA in EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, or RET genes were identified in community health systems, with data extracted from electronic health records. All pts were treated with at least one line of TKI. This cohort was assessed for overall survival (OS) in pts who did or did not receive ICI (either as a single agent or in combination with chemotherapy) at any time during their disease course. Sub-analyses were performed for pts with sensitizing GA in EGFR, and for pts treated with ICI after TKI therapy. 371 TKI-treated aNSCLC pts with sensitizing GA were included in the analysis, among whom 97 (26%) were treated with ICIs. Sensitizing GA were identified in EGFR (77%), ALK (15%), ROS1 (3%), BRAF (4%), NTRK1/2/3 (<1%), MET (3%), and RET (1%) genes. Pts who were in the ICI-treated vs ICI-naive groups had similar baseline characteristics with respect to histology (non-squamous vs squamous), initial stage at diagnosis, race/ethnicity, and never-smoking history. ICI-treated pts were younger (median age 62 vs 69), and more likely to be men (41% vs 34%). Compared to ICI-naive pts, those with ICI treatment anytime had greater OS for all pts with sensitizing GA (log-rank P=0.125), as well as for pts with EGFR GA (log-rank P=0.016) (Table). Compared to ICI-naive pts, those with ICI treatment after TKI therapy also had greater OS for all pts with sensitizing GA (log-rank P=0.179), as well as for pts with EGFR GA (log-rank P=0.025).Table 1ICI- naiveICI- treated anytimeLog-rank P-valueICI- treated after TKILog-rank P-valueNDiedMedian OS [95% CI], monthsNDiedMedian OS [95% CI], monthsNDiedMedian OS [95% CI], monthsAll TKI-treated patients27415923.8 [20.7, 28.6]976233.5 [28.9, 44.4]0.125614235.4 [29.7, 50]0.179TKI-treated patients with EGFR sensitizing GA21913721.4 [18.7, 26.3]684335.4 [29.7, 50]0.016493341.6 [29.7, 59.8]0.025 Open table in a new tab Longer OS was observed in TKI-treated aNSCLC pts with sensitizing GA who received ICI compared to those who did not receive ICI at any point. This was seen within pts with any sensitizing GA, and especially within the subset of pts with EGFR GA. Further analyses into determinants of treatment response in these real world pts should be explored, along with pursuing prospective clinical trials for ICI therapy in pts with aNSCLC and sensitizing GA.