Abstract 100P
Background
The outcome of advanced stage IV non-small cell lung cancer (NSCLC) with KRAS mutation warrants further evaluation in clinical practice.
Methods:We selected advanced stage IV KRAS mutant NSCLC discussed at the University Hospitals Leuven multidisciplinary tumour board between October 1, 2018, and October 31, 2022. Baseline and longitudinal treatment characteristics were collected. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods.
Results
We retrieved 142 patients (pts) of which 67 (47.1%) KRAS G12C and 75 (52.8%) KRAS non-G12C. Median and 2-year OS were 19.3 mo (95% CI 10.7–28.6) and 46% (95% CI 34–58) for G12C versus (vs) 22.7 mo (95%CI 12.4–32.5) and 47% (95%CI 35–57) for non-G12C (HR 1.01, 95%CI 0.75–1.60). In multivariate analysis WHO 0 and PD-L1 high were significant predictors of improved survival. At baseline, 1.5% of G12C and 1.3% of non-G12C were offered best supportive care, while 98.5% and 98.7% underwent first-line therapy including PD-1 inhibitor alone (28.4% vs 26.7%), platinum-doublet chemotherapy (PDC, 20.9% vs 26.7%) or PDC plus PD-1 inhibitor (49.3% vs 45.3%). Median PFS and 2-year PFS were 7.7 mo (95% CI 5.4–12) and 13% (95% CI 7–23) in G12C vs 8.4 mo (95% CI 6.4–11.0) and 26% (95% CI 17–37) in non-G12C (HR 1.20, 95% CI 0.85–1.71). At disease progression, second-line systemic therapy was given to 56.7% (n=38) of G12C and 49.3% (n=37) of non-G12C, and third-line systemic therapy to 32.8% (n=22) and 25.3% (n=19). PD(L)-1-based treatment, PDC or docetaxel-based therapy was given to 13.4% (n=9) KRAS G12C and 17.3% (n=13) KRAS non-G12C pts, 16.4% (n=11) and 13.3% (n=10), or 22.4% (n=15) and 24.0% (n=18) pts, respectively. Among docetaxel-treated pts, median PFS was 5.3 mo for G12C and 7.4 mo for non-G12C. KRAS inhibitors (sotorasib or opnurasib) were given in 18 (26%) G12C pts, with a median PFS of 7.6 mo.
Conclusions
In real-world 98% of pts with stage IV KRAS mutant NSCLC received first-line therapy and 53% received further line therapy. There was no influence of KRAS subtype (G12C vs non-G12C) on OS. At disease progression, a median PFS 5.2 mo for docetaxel-treated and 7.6mo for oral KRASi-treated was noted in KRAS G12C pts.
Clinical trial identification
MP025884.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.