Bevacizumab-based triplet versus doublet chemotherapy as first-line treatment for metastatic right-sided colon cancer: Results of the KCSG CO19-18 phase II trial.

Abstract

e15562 Background: The prognostic significance of primary tumor location in colorectal cancer has recently gained attention. Previous studies have demonstrated poorer outcomes of cetuximab-based therapy in right-sided colon cancer. Therefore, we conducted a multicenter, prospective, open-label, randomized phase II trial to evaluate the efficacy of bevacizumab plus FOLFOXIRI (A-FOLFOXIRI) versus bevacizumab plus FOLFOX/FOLFIRI (A-FOLFOX/FOLFIRI) in patients with unresectable right-sided colorectal cancer with poor prognosis (KCSG CO19-18; NCT03641976). Methods: Previously untreated patients with metastatic right-sided colon cancer (cecum to splenic flexure) were enrolled. Patients were stratified by ECOG performance status (0 vs 1–2), prior adjuvant chemotherapy (yes vs no), and participating center, and randomly assigned (1:1) to receive A-FOLFOXIRI (experimental arm) or A-FOLFOX/FOLFIRI (control arm). Treatment was administered every 2 weeks for up to 12 cycles, followed by investigator-determined continuation until disease progression, withdrawal of consent, or unacceptable toxicity. Maintenance therapy with bevacizumab, fluorouracil, and leucovorin was permitted in cases of intolerance to oxaliplatin or irinotecan. The primary endpoint was the 6-month progression-free survival (PFS) rate. Secondary endpoints included median overall survival, median PFS, objective response rate (ORR), and safety. Results: From December 2018 to February 2024, 61 patients were enrolled (median age, 62.9 years). At a median follow-up of 10.6 months, A-FOLFOXIRI did not significantly improve the 6-month PFS rate compared with A-FOLFOX/FOLFIRI (100% vs 87.1%; HR, 1.05; 95% CI, 0.53–1.71; p = 0.87). Median PFS was not significantly different between the two groups (14.7 months [95% CI, 10.3–19.1] vs 16.6 months [95% CI, 7.0–26.2]). The ORR was 82.8% versus 64.6%, respectively (p = 0.245). In an exploratory subgroup analysis, among patients who did not undergo palliative resection, A-FOLFOXIRI showed numerically longer PFS and higher ORR than A-FOLFOX/FOLFIRI. In contrast, among patients who underwent palliative resection, response rates were numerically higher across both treatment arms. The overall safety profiles were manageable in both arms. Grade ≥3 neutropenia was more frequent with A-FOLFOXIRI, whereas peripheral sensory neuropathy, gastrointestinal toxicities, and hypertension were comparable or slightly more frequent with A-FOLFOX/FOLFIRI. Conclusions: A-FOLFOXIRI did not improve PFS compared with A-FOLFOX/FOLFIRI in unresectable right-sided metastatic colorectal cancer, despite numerically higher overall response rates and an acceptable safety profile, underscoring the need for further studies to define patient subsets most likely to benefit from intensified chemotherapy. Clinical trial information: NCT03641976 .