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.
Purpose Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality despite advancements in targeted therapies. Monoclonal antibody medications—namely, bevacizumab, cetuximab, and panitumumab—are widely used in combination with chemotherapy as first-line treatments for unresectable mCRC in patients harboring wild-type KRAS tumors. However, the comparative effectiveness of these treatments in improving survival outcomes has not been clearly evaluated. This study aimed to directly compare the effectiveness of these 3 targeted therapies on survival outcomes in patients with unresectable mCRC.
Methods In this retrospective cohort study, we utilized Taiwan’s National Health Insurance Database and Taiwan Cancer Registry to identify patients newly diagnosed with mCRC who were treated with at least 6 cycles of bevacizumab, cetuximab, or panitumumab between 2011 and 2021. Propensity score overlap weighting was applied to adjust for baseline differences, and outcomes were evaluated using Cox proportional hazards models. Additionally, subgroup analyses were performed separately for left- and right-sided tumors.
Results Among 4,849 patients, treatment with cetuximab and panitumumab was associated with improved overall survival compared to bevacizumab, particularly in patients with left-sided tumors (adjusted hazard ratio, 0.77 and 0.75, respectively). Both cetuximab and panitumumab also showed significantly higher rates of conversion surgery, with panitumumab demonstrating the strongest effect. For right-sided tumors, however, the effectiveness of all 3 agents was limited, and no significant differences were observed in overall survival.
Conclusion Cetuximab and panitumumab were more effective than bevacizumab at improving survival outcomes and facilitating conversion surgery in left-sided mCRC. These findings highlight the importance of tumor laterality and molecular profiling in guiding therapeutic strategies.
Purpose Wild-type unresectable metastatic colorectal cancer (mCRC) poses challenges for treatment optimization. Effective first-line targeted therapies are crucial for improving outcomes, particularly when combined with second-line oxaliplatin-based chemotherapies. This study examined the effects of first-line cetuximab+FOLFIRI versus bevacizumab+FOLFIRI, followed by second-line oxaliplatin-based chemotherapy, on survival among patients with KRAS wild-type mCRC without primary tumor resection (PTR).
Methods A retrospective analysis of Taiwanese data (2013–2019) included patients with KRAS wild-type unresectable mCRC who received first-line cetuximab+FOLFIRI or bevacizumab+FOLFIRI, followed by second-line oxaliplatin-based chemotherapy. Survival outcomes—overall survival (OS) and time to treatment discontinuation (TTD)—were compared between these regimens using stabilized inverse probability of treatment weighting to adjust for potential confounders, followed by multivariate Cox proportional hazards regression analysis to account for clinical and biological variables.
Results In patients without PTR, first-line cetuximab+FOLFIRI with second-line oxaliplatin-based chemotherapy significantly improved OS from the start dates of first- and second-line treatment compared to first-line bevacizumab+FOLFIRI with second-line oxaliplatin-based therapy, yielding adjusted hazard ratios (HRs) of 0.60 (95% confidence interval [CI], 0.46–0.78) and 0.56 (95% CI, 0.42–0.73), respectively. No significant difference in TTD was observed (HR, 0.82; 95% CI, 0.65–1.04).
Conclusion First-line cetuximab+FOLFIRI followed by second-line oxaliplatin-based chemotherapy offers superior OS compared to bevacizumab+FOLFIRI followed by second-line oxaliplatin‑based chemotherapy in KRAS wild-type mCRC without PTR. These findings underscore the importance of personalized treatment sequencing, highlighting the need for further research to optimize mCRC management.