Response to immunotherapy in KRAS G12C mutated NSCLC: a single-centre retrospective observational study

Background: Non-small cell lung cancer is the leading cause of cancer death worldwide. New strategies in molecular therapies are being explored to detect and target genetic mutations in NSCLC. Therefore, it is also important to understand the interaction between these mutations and other therapies. This study focuses on possible correlations between the KRAS-G12C mutation and response of patients treated with immunotherapy.

Methods: Twenty-two patients with stage IV NSCLC undergoing immunotherapy were divided into two groups treated with first- and second-line therapy, respectively. KRAS-G12C mutation was detected by liquid biopsy Idylla KRAS assay.

Results: In first-line treated patients, there was no significant increase in PFS in patients with the KRAS mutation (20 months versus 14.5 months, HR = 1.31; CI 95% = 0.25-6.71; p value = 0.76) and no difference in OS (OS = 21 months, HR = 1; CI 95% = 0.17-6.2; p value > 0.99). In the second group, KRAS G12C mutated patients had a median PFS of 23 months compared with a median PFS of only 5 months among nonmutated patients (HR = 3.28; CI 95% = 0.86-12.5; p value = 0.03).

Conclusion: The results of this study do not reveal a clear correlation between mutation and response to immunotherapy. The mechanism regulating immune system activity in the tumor microenvironment remains unclear.