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This research evaluates the effectiveness of primary tumor resection and targeted therapies for survival in KRAS wild-type metastatic colorectal cancer.

February 28, 2026Open Access

Effectiveness of primary tumor resection for survival after first-line cetuximab or bevacizumab in KRAS wild-type metastatic colorectal cancer treated with subsequent trifluridine/tipiracil or regorafenib

Key Points

This research evaluates the effectiveness of primary tumor resection and targeted therapies for survival in KRAS wild-type metastatic colorectal cancer.
Retrospective cohort study using Taiwan's National Health Insurance Research Database.
Included patients diagnosed with metastatic colorectal cancer who received specific treatments.
Stratified patients based on primary tumor resection status.
Primary endpoints included overall survival and survival during subsequent treatments.
Used stabilized inverse probability of treatment weighting for adjustments.
Cetuximab showed longer survival (6.2 months) during later therapy than bevacizumab (4.9 months) in the non-PTR group.
Longer time to treatment discontinuation with cetuximab (11.8 months vs. 9.5 months) compared to bevacizumab in the non-PTR group.
Survival differences were less notable for patients who underwent primary tumor resection.

Abstract

Purpose: The optimal sequencing of targeted therapies and the role of primary tumor resection (PTR) in KRAS wild-type metastatic colorectal cancer (mCRC) remain unclear. This study compared survival outcomes in patients treated with first-line cetuximab plus FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) versus bevacizumab plus FOLFIRI, followed by second-line oxaliplatin-based chemotherapy and later-line trifluridine/tipiracil or regorafenib.Methods: This retrospective cohort study used Taiwan’s National Health Insurance Research Database and the Taiwan Cancer Registry. Patients diagnosed with mCRC between 2013 and 2019 were included if they received first-line cetuximab or bevacizumab plus FOLFIRI, followed by later-line trifluridine/tipiracil or regorafenib. Patients were stratified by PTR status. Primary endpoints were overall survival and survival during trifluridine/tipiracil or regorafenib treatment. Secondary endpoints included time to treatment discontinuation (TTD) and TTD during trifluridine/tipiracil or regorafenib therapy. Stabilized inverse probability of treatment weighting was used for adjustment.Results: Among 559 patients, 278 were assigned to the non-PTR group and 281 to the PTR group. In the non-PTR group, the cetuximab cohort demonstrated significantly longer survival during trifluridine/tipiracil or regorafenib therapy (6.2 months vs. 4.9 months; hazard ratio HR, 0.72) and longer TTD1 (the interval between initiation of first-line therapy and the start of second-line chemotherapy; 11.8 months vs. 9.5 months; HR, 0.67) than the bevacizumab cohort. Survival differences between regimens were less pronounced among patients who underwent PTR.Conclusion: First-line cetuximab plus FOLFIRI may confer a survival advantage over bevacizumab in patients with KRAS wild-type mCRC without PTR, including during later-line therapy with trifluridine/tipiracil or regorafenib, whereas bevacizumab appears to provide more consistent benefits in those with PTR.

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