| Title: |
FOLFIRI with cetuximab or bevacizumab in RAS wild-type metastatic colorectal cancer: Refining first-line treatment selection by combining clinical parameters: A post hoc analysis of the randomized open-label phase III trial FIRE-3/AIO KRK0306 |
| Authors: |
Holch, JW; Ohnmacht, AJ; Stintzing, S; Heinrich, K; Weiss, L; Probst, V; Stahler, A; Fischer von Weikersthal, L; Decker, T; Kiani, A; Kaiser, F; Heintges, T; Kahl, C; Kullmann, F; Link, H; Höffkes, HG; Moehler, M; Modest, DP; Menden, MP; Heinemann, V |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
Background: Primary tumor sidedness (PTS) with discrimination of left-sided (LC) and right-sided tumors (RC) guides patient selection for targeted first-line therapy in RAS wild-type (RAS-WT) metastatic colorectal cancer (mCRC). This study assessed the hypothesis whether considering PTS with additional clinical parameters better predicts the treatment benefit of targeted first-line treatment. Methods: In FIRE-3, first-line treatment with folinic acid, fluorouracil and irinotecan (FOLFIRI) plus cetuximab (FOLFIRI/Cet) was compared to FOLFIRI plus bevacizumab (FOLFIRI/Bev) in patients with RAS-WT mCRC and unresectable metastasis. We evaluated whether combining PTS with number of metastatic sites (NOM), liver-limited disease status (LLD), age, sex, or carcinoembryonic antigen level (CEA) better predicts treatment benefit regarding overall survival (OS). Here, Cox regression models with second-order interactions were applied. Further, the results were validated by policy learning and Lasso regression analysis. Findings: Among 400 RAS-WT mCRC patients, combining PTS with LLD status in a Cox regression model outperformed PTS alone for predicted treatment benefit (P = 0·005; c‑index=0·603). Significant OS benefit from FOLFIRI/Cet over FOLFIRI/Bev was observed in LC/non-LLD patients (HR=0·62; 95 %-confidence interval [CI]=0·46–0·82; P = 0·002), but mitigated in LC/LLD patients (HR=0·83; 95 %-CI=0·53–1·29; P = 0·400). In RC/non-LLD patients, FOLFIRI/Bev demonstrated a significant OS advantage over FOLFIRI/Cet (HR=2·09; 95 %‑CI=1·20–3·63; P = 0·010). However, RC/LLD patients showed potential benefit from FOLFIRI/Cet, though not statistically significant (HR=0·59; 95 %-CI=0·25–1·39; P = 0·218). Interpretation: Incorporating PTS and LLD status might improve selection of targeted first-line treatment in RAS-WT mCRC patients. FOLFIRI/Cet appears to be particularly beneficial for LC/non-LLD patients with mitigated benefit in patients with LC/LLD. In contrast, FOLFIRI/Bev is significantly favoured over FOLFIRI/Cet in patients ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0959-8049 |
| Relation: |
https://hdl.handle.net/11343/364687 |
| Availability: |
https://hdl.handle.net/11343/364687 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.F72ED502 |
| Database: |
BASE |