Phase II study of irinotecan liposome combined with 5-FU/LV + bevacizumab as first-line therapy in metastatic colorectal cancer: An early analysis from the study.

e15566 Background: FOLFIRI combined with bevacizumab is a standard treatment as first-line therapy in metastatic colorectal cancer (mCRC). Irinotecan liposome is a nanoliposomal formulation of irinotecan which has improved pharmacokinetics (PK) and tumor distribution of irinotecan and its active metabolite, SN-38. This phase II study was designed to evaluate the safety and efficacy of irinotecan liposome combined with 5-FU/LV+ bevacizumab as first-line therapy in mCRC patients. Methods: Patients with RAS/BRAF V600E mutant or right half mCRC and no prior treatment for metastatic disease were eligible for this study. All patients underwent UGT1A1 genotyping to guide irinotecan liposome dose. Eligible patients received irinotecan liposome (70 mg/m² for wild-type or heterozygous UGT1A1*6 or *28; 50 mg/m² for double heterozygous UGT1A1*6 and *28 or homozygous UGT1A1*6 or *28) +5-FU (400 mg/m² bolus, then 2400 mg/m² infusion)/LV (400 mg/m²)+ bevacizumab (5 mg/kg) every 2 weeks until disease progression, unacceptable toxicity or completion of eight cycles of treatment. The primary endpoint is objective response rate (ORR), and secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: From May 2024 to December 2024, 29 patients were enrolled in the study. Media age was 60 (range: 40-72) years, 51.7% patients were male and 24.1% had more than 2 metastatic sites. 51.7% of the tumors were located in the right colon, 17.2% in the left colon and 31.0% in the rectum. The median number of treatment cycles administered was 7 (range 1-8). At the time of this report, 12 patients discontinued treatment due to completion of eight cycles of treatment (n = 7), surgery (n = 4), or unable to tolerate the next cycle of treatment (n = 1). 22 patients underwent at least one tumor assessment. Among them, 14 patients achieved partial response, 8 patients achieved stable disease. The ORR was 63.6% (95%CI 40.7%-82.8%) and the DCR was 100.0% (95%CI 84.6%-100.0%). Median PFS and median OS were not reached yet. Treatment-related adverse events (TRAEs) occurred in 29 patients (100.0%), and 13 patients (44.8%) experienced grade 3-4 AEs. Grade 3-4 TRAEs in ≥ 10% patients included neutropenia (34.5%), leucopenia (17.2%), diarrhea (17.2%), nausea (17.2%), and vomiting (10.3%). No unexpected adverse events and grade 5 TRAE occurred. Conclusions: The results showed that irinotecan liposome combined with 5-FU/LV+ bevacizumab has promising efficacy and controllable safety as first-line therapy in metastatic colorectal cancer, and is worthy of further treatment and follow-up. Clinical trial information: NCT06341296 .