Bevacizumab, TAS-102, and irinotecan in oxaliplatin and fluoropyrimidine pre-treated metastatic colorectal cancer (BEV-TASIRI): A single-arm, prospective, multicenter study and comparison with BEV-FOLFIRI/XELIRI using inverse probability of treatment

e15571 Background: The efficacy of second line bevacizumab and FOLFIRI or irinotecan is limited for metastatic colorectal cancer (mCRC) after oxaliplatin and fluoropyrimidine treatment. TAS-102 is a novel oral antimetabolite that can overcome resistance to fluoropyrimidine. A few single arm studies had demonstrated that the combination of irinotecan, TAS-102 and bevacizumab was generally tolerated and a trend to extend progression free survival (PFS). Methods: BEV-TASIRI is a multicenter, single-arm prospective study. Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine were eligible for treatment with bevacizumab (5mg/kg), irinotecan (150 mg/m 2 ), and TAS-102 (30 mg/m 2 , bid, d1-5 , ) in 14-day cycles. The primary endpoint was PFS. Inverse Probability of Treatment Weighting (IPTW) analysis was used to compare the PFS between patients treated with BEV-TASIRI and parallel cohort (BEV-FOLFIRI/XELIRI) during the same time period. Results: From October 24 th 2022 to December 31 st 2024, 37 of planned 50 patients were enrolled. The median age was 62 years old and 23 were males. 27 patients had RAS/BRAF mutation. 9 patients were right-sided. All patients received at least one cycle of treatment. Among 32 evaluable patients, 7 achieved PR, 22 reached SD and 3 had PD, with the ORR of 21.8% and DCR of 90.6% respectively. The median PFS was 7.7months (95% CI: 4.8-10.6). The median OS was not reached. 25 (67.6%) patients in BEV-TASIRI had grade ≥3 TRAEs, which were predominantly neutropenia (43.2%). The most common non-hematological AE were nausea (66.7%), vomiting (16.7%) and alanine aminotransferase increased (16.4%). 14 patients (38.9%) had TAS-102 dose reduction from 30mg/m 2 to 25mg/m 2 and 18 patients (50.0%) had irinotecan dose reduction from 150mg/m 2 to125 mg/m 2 . After IPTW, 57 patients in BEV-FOLFIRI/XELIRI as control were analyzed with dosage at physician’s decision. When compared with BEV-TASIRI arm, the ORR and DCR in the control cohort were 10.5% (p = 0.053) and 70.2% (p = 0.027). The median PFS was 4.8 months (95% CI: 3.9-6.0, p = 0.022). Grade ≥3 TRAEs occurred in 10 (17.5%, p < 0.001) patients, of whom 5 had neutropenia (8.7%, p < 0.001). Conclusions: In patients with mCRC who progressed after oxaliplatin and fluoropyrimidine treatment, bevacizumab plus irinotecan and trifluridine-tipiracil (BEV-TASIRI) exhibited promising and superior ORR, DCR and PFS, but at a cost of more neutropenia, when compared to bevacizumab plus FOLFIRI/XELIRI. Clinical trial information: NCT06242067 .