Combination of oral fluoropyrimidines and EGFR-directed antibodies in frail patients with metastatic colorectal cancer: a systematic review.
4 affiliations
- 1Department of Hematology, Oncology and Cancer Immunology (CCM), Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
- 2German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
- 3Department of Hematology, Oncology and Cancer Immunology (CCM), Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Charitéplatz 1, 10117, Berlin, Germany. [email protected].
- 4German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ), Heidelberg, Germany. [email protected].
Abstract
Background
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.Methods
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.Results
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.Conclusion
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.
Related
- [Comment] Tumor debulking in combination with chemotherapy in multiorgan metastatic colorectal cancer: the ORCHESTRA randomized clinical trial
- Efficacy and safety of regorafenib plus PD-1/PD-L1 inhibitors for metastatic colorectal cancer: a systematic review and meta-analysis
- Comparative efficacy of fruquintinib, regorafenib or TAS-102 in patients with KRAS-mutant metastatic colorectal cancer: a systematic review and network meta-analysis
- Comparative effectiveness of first-/second-generation EGFR-TKI combination therapy versus third-generation EGFR-TKI monotherapy in untreated locally advanced or metastatic EGFR-mutant NSCLC: a real-world, retrospective study in China
- 1189 A phase 1/1b study of the tumor-activated IL-2 prodrug WTX-124 alone or in combination with pembrolizumab in adults with relapsed/refractory, advanced/metastatic, immunotherapy-sensitive solid tumors
BibTeX
@article{hasenburg2026combination,
title = {{Combination of oral fluoropyrimidines and EGFR-directed antibodies in frail patients with metastatic colorectal cancer: a systematic review.}},
author = {Alena Annbalou Hasenburg and Sebastian Stintzing and Arndt Stahler},
journal = {Journal of cancer research and clinical oncology},
year = {2026},
month = oct,
doi = {10.1007/s00432-026-06639-x},
url = {https://europepmc.org/article/MED/42902018},
note = {CC BY},
}
RIS
TY - JOUR
TI - Combination of oral fluoropyrimidines and EGFR-directed antibodies in frail patients with metastatic colorectal cancer: a systematic review.
AU - Alena Annbalou Hasenburg
AU - Sebastian Stintzing
AU - Arndt Stahler
PY - 2026
DA - 2026/10/20
JO - Journal of cancer research and clinical oncology
DO - 10.1007/s00432-026-06639-x
UR - https://europepmc.org/article/MED/42902018
AB - Background 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.Methods 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.Results 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.Conclusion 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.
SN - 0171-5216
SN - 1432-1335
ER -