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

The analysis included seven eligible publications with a combined total of 262 patients and evaluated oral fluoropyrimidines used with cetuximab or panitumumab across treatment lines in people considered unfit for combination therapy. Prospective trials are needed to confirm the findings. The researchers searched PubMed and the Cochrane Library for phase II and phase III studies of capecitabine, S-1, or trifluridine/tipiracil combined with an EGFR-directed monoclonal antibody.

The review covered efficacy and safety outcomes for metastatic colorectal cancer and considered evidence in the first line and in the third line or beyond. First-line evidence was limited to elderly cohorts receiving capecitabine with an EGFR-directed antibody. Among those treated with capecitabine plus cetuximab, median progression-free survival was 7.2 months and median overall survival was 17.1 months.

In the cohort receiving capecitabine plus panitumumab, the corresponding medians were 7.5 and 23.7 months. Indeed, the review’s conclusion cautioned that capecitabine should not be used together with anti-EGFR antibodies. In studies of third-line or later treatment, median progression-free survival ranged from 2.4 months for trifluridine/tipiracil plus cetuximab to 5.8 months for trifluridine/tipiracil plus panitumumab.

Median overall survival ranged from 9.8 to 14.2 months, respectively. S-1 plus cetuximab was associated with a median progression-free survival of 5.5 months and median overall survival of 13.6 months. The authors described the toxicity profile of trifluridine/tipiracil combined with an EGFR-directed antibody as manageable in the available evidence for RAS wild-type metastatic colorectal cancer, identifying this approach as feasible and promising for some frail patients.

The small number of publications, combined population of 262 participants, and limited first-line evidence mean that the reported activity requires confirmation in prospective studies.

Subject of Research: Systematic review of oral fluoropyrimidines with EGFR-directed antibodies in frail metastatic colorectal cancer

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

Article References: Hasenburg, A. A., Stintzing, S., & Stahler, A. (2026). Combination of oral fluoropyrimidines and EGFR-directed antibodies in frail patients with metastatic colorectal cancer: a systematic review. Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-026-06639-x

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DOI: 10.1007/s00432-026-06639-x

Keywords: metastatic colorectal cancer, frail patients, systematic review, trifluridine/tipiracil, EGFR antibodies, cetuximab, panitumumab, capecitabine, S-1, RAS wild-type, Combination, oral