AUTHOR=Peng Lixiu , Guo Jun , Kong Li , Huang Yong , Tang Ning , Zhang Juguang , Wang Minglei , He Xiaohan , Li Zhenzhen , Peng Yonggang , Wang Zhehai , Han Xiao 

TITLE=Efficacy of immunotherapy in KRAS-mutant advanced NSCLC: A real-world study in a Chinese population

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1070761

DOI=10.3389/fonc.2022.1070761

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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 (<italic>KRAS</italic>) 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 <italic>KRAS</italic>-mutant NSCLC in a Chinese cohort.</p></sec><sec><title>Methods</title><p>In this retrospective cohort study, we extracted the clinical, molecular, and pathologic data from the electronic health records of patients with advanced <italic>KRAS</italic>-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.</p></sec><sec><title>Results</title><p>Between January 2018 and November 2020, 793 patients were identified with stage IIIB-IV NSCLC and a total of 122 patients with <italic>KRAS</italic> 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; <italic>P</italic>=1.81E-05), with no statistical difference observed in the mPFS (10.5 vs. 8.2 months; <italic>P</italic>=0.706). Patients receiving immunotherapy-based regimens either in the first line (<italic>P</italic>=0.00038, <italic>P</italic>=0.010, respectively) or second-line setting (<italic>P</italic>=0.010, <italic>P</italic>=0.026, respectively) showed benefits in both PFS and OS. Subgroup analysis indicated that in patients having <italic>KRAS</italic> G12C or non-<italic>KRAS</italic> G12C mutant types, immunotherapy showed benefits of better OS (<italic>P</italic>=0.0037, <italic>P</italic>=0.020, respectively) than chemotherapy. Moreover, in advanced NSCLCs patients with or without <italic>KRAS/TP53</italic> co-mutation the immunotherapy-based regimen achieved longer OS and PFS than chemotherapy-based regimens.</p></sec><sec><title>Conclusions</title><p>In the Chinese population of patients with <italic>KRAS</italic>-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 <italic>KRAS</italic> mutational subtypes.</p></sec>