Triplet chemotherapy plus cetuximab as first-line treatment in extended RAS wild-type metastatic colorectal cancer patients

Background: Triplet chemotherapy plus cetuximab showed promising results in phase II trials in unsystematically selected RAS population. We evaluated FOLFIRINOX + cetuximab efficacy as first-line treatment in extended RAS wild-type metastatic colorectal cancer (mCRC) patients. Methods: We retrospectively analyzed patients treated with FOLFIRINOX + cetuximab, using data from clinical trials and real-life practice. Extended mutation analysis was performed when RAS/BRAF status was unavailable. The primary endpoint was progression-free survival (PFS). Results: Seventy patients (61.4 % male, median age 58.7 years) were analyzed. Eighty percent had leftsided mCRC and 97.1 % had liver metastases. Median PFS and overall survival (OS) were 13.3 and 48.5 months, respectively. The objective response rate was 85.7 %, with 20 % complete response. Primary tumor location did not affect OS and PFS. BRAF wild-type patients ( n = 65) had longer PFS (13.3 vs. 6.0 months; p = 0.005) and OS (50.1 vs. 21.2 months; p = 0.007) than BRAF mutated patients ( n = 5, including four BRAFV600E ). Median OS was significantly longer in resected patients ( n = 39, 55.1 vs. 30.7 months; p = 0.030). Main toxicities were diarrhea (31.4 %) and neutropenia (21.4 %). Conclusion: FOLFIRINOX + cetuximab provides good PFS, high response rate and prolonged disease control in initially unresectable extended RAS wild-type mCRC. This combination is particularly interesting for selected patients with liver-limited disease eligible to secondary resection. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )