Treatment patterns and outcomes in KRASG12C-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study

Abstract

Objectives: KRAS mutations, particularly KRAS^G12C, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS^G12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRAS^G12C-positive advanced NSCLC receiving systemic therapy post-ICI treatment.

Methods: From the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with KRAS^G12C-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models.

Results: The patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRAS^G12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, p = 0.012).

Conclusion: This study contributes valuable real-world data on KRAS^G12C-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRAS^G12C-targeted therapies.

Keywords: Advanced NSCLC; Immune checkpoint inhibitors; Immunotherapy; KRAS(G12C); Non-small cell lung cancer; Real-world data; Sotorasib; Systemic therapy; Targeted therapy; Treatment patterns.