Abstract 1312P
Background
KRAS gene mutations are found in 20-30% of NSCLC. The prognostic value of KRAS status in NSCLC is still controversial, and may be affected by mutation subtypes. Moreover, KRAS mutations have been associated with increased programmed death-ligand 1 (PD-L1) expression, high tumor mutation burden and might be associated with greater benefit from ICI. Therefore, we explored the prognostic impact of KRAS mutations in patients with advanced NSCLC treated with ICI monotherapy.
Methods
We reviewed data of 227 consecutive patients with advanced NSCLC treated with ICI monotherapy at our institution from January 2016 to March 2021. The prognostic impact of KRAS status was investigated through Kaplan-Meier and Cox-regression methods in terms of both progression-free survival (PFS) and overall survival (OS).
Results
Overall, 169 patients with known KRAS variant status were included in the analysis. Of these patients, 95% were stage IV, 83% were smokers, and 83% had a diagnosis of adenocarcinoma. PD-L1 status was negative in 25% of cases and 58% had a tumor proportional score ≥50%. KRAS mutations were identified in about 30% of patients (50/169). The most frequent molecular alteration was codon 12 mutation (n=44; 25 patients with KRASG12C mutations), followed by codon 3 (n=4) and codon 61 (n=2) mutations. The 38% of patients were treated with ICI monotherapy at first-line and 15% after at least two prior treatment lines. In our cohort, patients with KRAS mutations were found to have better OS (26.94 vs. 12.02 months, HR 0.63, 95% CI 0.42-0.93, p=0.02) and PFS (6.76 vs. 3.84 months, HR 0.68, 95% CI 0.47-0.98, p=0.04) compared with patients without KRAS mutations. In contrast, no difference in terms of OS (HR 1.07, 95% CI 0.50-2.30, p=0.85) and PFS (HR1.29, 95% CI 0.64-2.62, p=0.47) was detected between patients with KRASG12C vs. KRASnon-G12C mutations. The independent prognostic value of KRAS mutations was confirmed through multivariate cox-regression analysis in terms of OS (HR 0.59, 95% IC 0.37-0.94, p=0.02) but not PFS (HR 1.39, 95% CI 0.93-2.08, p=0.10).
Conclusions
KRAS mutations are associated with prolonged survival in patients with NSCLC treated with ICI monotherapy, with no differences according to mutation subtypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Pelizzari: Financial Interests, Personal, Expert Testimony: MSD. A. Follador: Financial Interests, Personal, Advisory Board, Travel expenses: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Travel expenses: Eisai. All other authors have declared no conflicts of interest.