RAS mutation specific survival in patients with metastatic colorectal cancer treated with trifluridine/tipiracil.

Abstract

197 Background: Trifluridine/tipiracil (T/T) is effective in patients with pretreated metastatic colorectal cancer (mCRC). RAS mutational status could predict magnitude of T/T effect (van de Haar et al, Nat Med. 2023), but the data are conflicting. Methods: We retrospectively reviewed the clinical data of 402 patients consecutively treated with T/T in two institutions in the Czech Republic and analysed the potential predictive value of different RAS mutations. Results: Baseline characteristics: median age 65 (range 28-84), female 32.8%, ECOG PS 0 in 32.8% and 1 in 64.9%, primary tumor location left colon in 76.3%. The median line in which T/T was administered was 3 (range 2-8). Median number of T/T cycles administered was 3 (range 2-27). Median follow-up was 32.4 months, 358 patients died (89.1%). Overall survival (OS) was 9.3 months (95% CI 8.7 to 10.3) and progression-free survival (PFS) 3.5 months (3.2 to 3.6). RAS mutation was detected in 54.2% patients. KRAS G12 mutation was found in 117 patients (29.1%), KRAS G13 in 19 (4.7%), other RAS mutation in 25 (6.2%), non-specified RAS mutation in 57 (14.2%), and BRAF mutation in 14 (4.8%). No difference in OS in RAS wildtype (wt) vs mutated group (P=.50) was observed. OS in the defined groups was found: wtRAS group (9.1 months), KRAS G12 (9.1 m), KRAS G13 (5.6 m), and other RAS mutations (10.6 m, P=.180). Patients with KRAS G13 had worse OS vs all other patients (P=.029; HR 1.97), vs wt (P=.02; HR 2.08), vs other mutated (P=0.067; HR 1.75), vs KRAS G12 mutated patients (P=.069; HR 1.75). Patients with KRAS G12 had no OS difference vs other groups of patients. In KRAS G12 group we found that specific gene variants have different OS (for G12C, 7 patients, OS was 6.0 months; for G12D, 41 patients, 9.0 m; for G12V, 45 patients, 10.5 m; for G12S, 7 patients, 16.1 m; for G12A, 11 patients, 7.6; other G12 variants, 5 patients, 10.0 months, P=.028). BRAF mutation was associated with worse OS (6.6 vs 9.1 months, P=.02, HR 2.46). Conclusions: We did not confirm the negative predictive value of KRAS G12 mutation in patients treated with T/T, however, OS depends on the specific G12 mutation. In contrast, patients with KRAS G13 mutation had worse survival.