This study aimed to evaluate the impact of KRAS status on the efficacy of first-line immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC).
Patients with advanced incurable or metastatic NSCLC with PD-L1 ≥50% treated with palliative-intent, single-agent PD-1/PD-L1 inhibitors at the Cancer Centre of Southeastern Ontario were included. KRAS mutation status was determined via massively parallel sequencing. Primary study outcome was median overall survival (mOS).
Seventy-eight patients (59 non-squamous, 19 squamous) were identified; only non-squamous patients were included in KRAS mutation analyses. Thirty patients (51%) were KRAS-MT (mutant), with G12C (19%), G12V (15%), and G12D (13%) accounting for the most common KRAS mutation subtypes. There was no difference in mOS between KRAS-MT and KRAS-WT (wild-type) patients (12.9 vs. 19.3 months, p = 0.879). There was a non-significant trend towards worse mOS in KRAS G12C patients compared to non-G12C and KRAS-WT patients (11.4 vs. 44.9 vs. 19.3 months, p = 0.772). On multivariable analysis, KRAS-MT status was not associated with mOS (HR 0.901, 95%CI 0.417-1.946, p = 0.791). ECOG≥2 was an independent prognostic factor for worse mOS (HR 2.853, 95%CI 1.237-6.583, p = 0.014). Immune-related adverse events did not differ between KRAS-MT and KRAS-WT groups (48% vs. 52%, p = 1.000).
KRAS mutation status did not have a significant impact on ICI efficacy or safety. However, a non-significant trend towards worse survival was noted in patients treated with ICI whose tumours harboured the KRAS G12C variant. This study provides valuable information for comparative analysis in the future.

References

PubMed