Efficacy of ramucirumab and docetaxel given either before or after immune checkpoint inhibitors in patients with lung cancers.

Abstract

9078 Background: Ramucirumab and docetaxel (RamDoce) is a treatment for lung cancer patients after platinum-based therapy regardless of histology, the presence of oncogenic drivers, or prior immune checkpoint inhibition (ICI). Past data has shown a possible differential response to chemotherapy based on ICI exposure. We determined the activity of RamDoce given to patients before or after ICI. Methods: We evaluated patients with stage IV lung cancers who received RamDoce at MSK from 1/2015 - 6/2018. We grouped them based on timing of RamDoce: Before (including never receiving ICI) or After ICI. Ram was given at 8-10mg/kg with Doce 60-75mg/m2 every 2-3 weeks. Demographics, oncogene status and histologic comparisons were done with Mann-Whitney and Fisher’s exact tests. Time to treatment discontinuation (TTD) and overall survival (OS), were compared by long-rank test. Results: 194 patients received RamDoce: 78 Before and 116 After ICI. Median line of therapy for RamDoce in both cohorts was 3. Demographics in the Before and After ICI respectively included: 45 vs 53 female (p = 0.56), 50 vs 96 ever-smokers (p = 0.004), 59 vs 64 years old (p = 0.003), 73 vs 103 adenocarcinoma (p = 0.30). 83% (64/77) of patients with available tissue were PD-L1 negative. TMB was similar between cohorts (7.8 vs 6.1 mut/Mb, p = 0.68). Before ICI had a greater proportion of oncogenes present (64% vs 47%, p = 0.02). Combining Cohorts, TTD for EGFR-mutant (n = 41) and KRAS-mutant (n = 45) lung cancers was 4.0 and 3.9 months respectively vs 2.3 months for EGFR/KRAS-WT (p = 0.051). There was no difference in TTD for adenocarcinoma (n = 176) vs squamous cancers (n = 15, 2.6 vs. 3.1 months respectively; HR 0.8, 95% CI 0.4-1.7, p = 0.51). We saw no difference in TTD between Before (1.5 months) and After ICI (3.0 months, HR 0.88, 95% CI 0.7-1.2, p = 0.39). There was no difference in OS: Before ICI (1.6 years) and After ICI (2.0 years; HR 1.1, 95% CI 0.8-1.5, p = 0.49). Conclusions: There was no difference in TTD or OS for RamDoce when given before or after ICI. There was a trend toward prolonged benefit from RamDoce in EGFR/KRAS-mutant lung cancers. Data on the efficacy of RamDoce in oncogene-driven groups can help guide care and serve as a benchmark for new drug evaluations.