Combination of oral fluoropyrimidines and EGFR-directed antibodies in frail patients with metastatic colorectal cancer: a systematic review.

Authors

Alena Annbalou Hasenburg, Sebastian Stintzing, Arndt Stahler

Published in

Journal of cancer research and clinical oncology. Volume 152. Issue 10. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Evidence of treatment strategies in frail patients (i.e. not fit for combination therapies) with unresectable metastatic colorectal cancer (mCRC) is limited to dose-reduced doublet regimens or oral fluoropyrimidines (FP) with bevacizumab. We conducted a systematic review analyzing evidence for oral FPs with epidermal growth factor receptor (EGFR)-directed monoclonal antibodies for patients with RAS wild-type (WT) mCRC across treatment lines.
We searched PubMed and Cochrane Library for phase II and phase III studies evaluating oral FPs (capecitabine, S-1 or trifluridine/tipiracil (FTD/TPI)) plus EGFR-directed monoclonal antibody (panitumumab or cetuximab) in mCRC. Outcomes included efficacy and safety.
Seven publications met inclusion criteria (n = 262 patients). First-line data was limited to elderly cohorts receiving capecitabine plus cetuximab or panitumumab with a median progression-free survival (PFS)/median overall survival (OS) of 7.2/17.1 months (cetuximab) and 7.5/23.7 months (panitumumab), respectively. In third-line and beyond, median PFS for the combination of FTD/TPI plus cetuximab or panitumumab ranged from 2.4 (cetuximab) to 5.8 months (panitumumab), and OS from 9.8 (cetuximab) to 14.2 months (panitumumab). S-1 plus cetuximab was associated with a median PFS of 5.5 months and OS of 13.6 months.
While capecitabine should not be used together with anti-EGFR antibodies, FTD/TPI in combination with an EGFR-directed antibody appears feasible, shows promising activity and manageable toxicity profile in RAS WT mCRC potentially offering an alternative for frail patients; prospective trials are needed.

PMID:
42902018
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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