Adjuvant chemotherapy with mFOLFOXIRI versus mFOLFOX6 in MRD-positive stage II-III colorectal cancer.

Abstract

TPS3642 Background: About 25% to 30% of resectable high-risk stage II and stage III colon cancers might relapse after radical resection and adjuvant chemotherapy with FOLFOX regimen. Recent studies have underscored the significance of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD), representing a residual presence of cancer cells, as a prognostic factor for postoperative recurrence in CRC. Patients exhibiting positive MRD predicted a considerable high risk of recurrence and metastasis, even after adjuvant chemotherapy. In the realm of postoperative adjuvant chemotherapy, Comparing with FOLFOX, whether the early introduction of intensified chemotherapy, mFOLFOXIRI, could further eradicate MRD and improve the long-term prognosis remains unclear. Methods: This multicenter phase III study (NCT05427669) plans to enroll 340 colorectal cancer patients with MRD positive after curative-intent R0 surgical resection, age 18 to 70 years, ECOG performance status 0-1. Patients were randomized (1:1) to receive mFOLFOXIRI (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m², and 5-FU 2.4 g/m²over 46 h) or mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m2 then 2.4 g/m² over 46 h) every two weeks for 24 weeks (12 cycles). Patients will be followed for 5 years after the end of adjuvant chemotherapy. The primary endpoint was 3-year DFS. A gain of 14% in 3-yr DFS is expected (74% in the experimental arm vs. 60% in the control arm; α, 5% [two-sided log-rank test]; 1-β, 80%). Secondary endpoints included overall survival, 3-year distant metastasis-free survival, QoL and toxicity. Clinical trial information: NCT05427669 .