Efficacy of immunotherapy in KRAS-mutant advanced NSCLC: A real-world study in a Chinese population
Lixiu Peng, Jun Guo, Li Kong, Yong Huang, Ning Tang, Juguang Zhang, Minglei Wang, Xiaohan He, Zhenzhen Li, Yonggang Peng, Zhehai Wang, Xiao Han
Abstract
Background Immunotherapy has improved the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC). However, in patients with Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations, the superior efficacy of immunotherapy has not been elucidated and especially in real-world practice. Our study aimed to use real-world data to assess the efficacy of immunotherapy in KRAS -mutant NSCLC in a Chinese cohort. Methods In this retrospective cohort study, we extracted the clinical, molecular, and pathologic data from the electronic health records of patients with advanced KRAS -mutant NSCLC at Shandong Cancer Hospital between January 2018 and May 2022. Furthermore, we evaluated the progression-free survival (PFS) and overall survival (OS) of the included patients. Results Between January 2018 and November 2020, 793 patients were identified with stage IIIB-IV NSCLC and a total of 122 patients with KRAS mutations were included in the analysis. The majority of patients were diagnosed with stage IV (82.0%) adenocarcinoma (93.4%), along with a history of smoking (57.4%). Of these, 42% of patients received anti-PD-(L)1 with or without chemotherapy (Immunotherapy-based regimens), while 58.2% of patients received chemotherapy (Chemotherapy-based regimens). The median overall survival (mOS) in this cohort was 22.9 months (95% CI: 14.1–31.7), while the median-progression-free survival (mPFS) was 9.4 months (95% CI: 6.6–12.1). Patients receiving immunotherapy-based regimens displayed better mOS than those receiving chemotherapy-based regimens (45.2 vs. 11.3 months; P =1.81E-05), with no statistical difference observed in the mPFS (10.5 vs. 8.2 months; P =0.706). Patients receiving immunotherapy-based regimens either in the first line ( P =0.00038, P =0.010, respectively) or second-line setting ( P =0.010, P =0.026, respectively) showed benefits in both PFS and OS. Subgroup analysis indicated that in patients having KRAS G12C or non- KRAS G12C mutant types, immunotherapy showed benefits of better OS ( P =0.0037, P =0.020, respectively) than chemotherapy. Moreover, in advanced NSCLCs patients with or without KRAS/TP53 co-mutation the immunotherapy-based regimen achieved longer OS and PFS than chemotherapy-based regimens. Conclusions In the Chinese population of patients with KRAS -mutant advanced NSCLC, immunotherapy-based regimens achieved longer OS than chemotherapy-based regimens, which was independent of first or second-line setting, as well as KRAS mutational subtypes.