Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC)

Abstract

ObjectivesTo evaluate the comparative effectiveness of sotorasib monotherapy versus docetaxel as monotherapy or combination therapy in patients with pretreated KRAS G12C-mutated advanced NSCLC in the real-world. MethodsA US-based electronic health record–derived de-identified database was used in this study. Patients with pretreated KRAS G12C-mutated advanced NSCLC who initiated sotorasib between May 28, 2021 and September 30, 2022, and docetaxel between January 01, 2019 and September 30, 2022 (to enhance sample size), were included, with a minimum of 12-month opportunity for follow-up. Treatment groups were balanced via overlap weighting propensity score methods. Median OS in the 2L and 2L+settings were calculated using Kaplan-Meier estimates. Hazard ratios (HR) were estimated via Cox proportional hazard models. ResultsOverall, the clinical characteristics in sotorasib and docetaxel cohorts were balanced after propensity score weighting. At baseline, most patients were > 65 years of age, had ECOG performance status of 0–1, were from the community practice setting, had advanced stage at initial diagnosis, and had prior anti-PD-(L)1 treatment and/or platinum-based chemotherapy. In the 2L setting, the median OS (95 % CI) for sotorasib (N=102) and docetaxel (N=58) patients was 10.2 (7.6–16.3) and 6.0 (4.2–11.0) months, respectively, with a corresponding mortality HR (95 % CI) of 0.62 (0.41–0.93). In the 2L+setting, the median OS (95 % CI) for sotorasib (N=164) and docetaxel (N=116) was 10.2 (8.0–14.6) and 7.2 (5.1–10.6) months, respectively, with a corresponding mortality HR (95 % CI) of 0.65 (0.49–0.87). In patients with prior anti-PD-(L)1 treatment, the mortality HR (95 % CI) in the sotorasib group versus docetaxel was 0.61 (0.39–0.94) and 0.65 (0.48–0.89) in the 2L and 2L+setting, respectively. Findings from other subgroups were consistent with the primary analyses. ConclusionIn this real-world comparative analysis of patients with pretreated KRAS G12C-mutated advanced NSCLC, sotorasib monotherapy demonstrated a longer median OS compared to docetaxel monotherapy or combination therapy.