P-149 QUATTRO-II: A multicenter randomized trial comparing CAPOXIRI + bevacizumab with FOLFOXIRI + bevacizumab as first-line treatment in patients with metastatic colorectal cancer: Efficacy and safety analysis

FOLFOXIRI + bevacizumab (BEV) is a highly effective first-line treatment for patients with metastatic colorectal cancer (mCRC). However, high incidences of hematologic adverse events (AEs) and pump infusion of 5-FU q2wk can complicate treatment continuation. Given that capecitabine (CAP), an oral fluoropyrimidine, can be administered every 3weeks without using a port infusion, CAPOXIRI + BEV may be a more convenient regimen compared with FOLFOXIRI + BEV if without compromising the efficacy. QUATTRO-II (NCT 04097444) was an open-label, multicenter, randomized phase II study that evaluated the efficacy and safety of CAPOXIRI + BEV (Arm B) versus FOLFOXIRI + BEV (Arm A). Here, we show the efficacy and safety endpoints. Patients were randomly allocated to Arms A or B at a 1:1 ratio. Induction treatment in Arm A/B was continued for 8/6 cycles (12/8 cycles at maximum if feasible), followed by the maintenance treatment of either 5-FU + leucovorin + BEV or CAP + BEV upon discontinuation by the investigators. The primary endpoint was progression-free survival (PFS) censored for resected cases, and the secondary endpoints were overall survival (OS), overall response rate (ORR), R0 resection rate, early tumor response (ETS), depth of response (DpR), and safety. Furthermore, as an additional analysis, modified PFS was calculated based on the PFS definition in the TRIBE study (FOLFOXIRI + BEV vs. Doublet + BEV; phase 3, NCT00719797) to follow patients until progressive disease or death without censoring surgery. From June 2020 to June 2021, 103 patients were randomly assigned to a corresponding arm (Arm A/B, 51/52 patients). Baseline characteristics, including age (median, 60 years in both arms) and Eastern Cooperative Oncology Group performance status of 0 (90%/94%), were similar between the arms. With a median follow-up of 24.1 months, the median PFS (Arm A/B) was 10.6 months (95% CI 7.7–13.3)/10.9 months (95% CI 9.3–14.3; HR 1.114, P = 0.654) (HR: 0.8 < 1.114 < 1.25). The median modified PFS was 11.2 months (95% CI: 9.0–14.9)/13.4 months (95% CI: 10.0–15.2; HR = 0.959, and P = 0.847). The 2-year OS rate (Arm A/B) was 65.5% (95% CI 49.5–77.6)/74.3% (95% CI 59.8–84.2), and the median OS was not reached. Moreover, the ORR was 76.5%/84.6%; the R0 resection rate was 21.6%/26.9%; ETS achieved in 71.4%/82.0% of patients; and the median DpR was 43.0%/53.7%. Incidences of major adverse events (grade ≥3, Arm A/B) were as follows: neutropenia (68.6%/40.4%), febrile neutropenia (9.8%/11.5%), diarrhea (7.8%/17.3%), and appetite loss (7.8%/17.3%). No treatment-related deaths occurred. The efficacy of CAPOXIRI + BEV was comparable to that of FOLFOXIRI + BEV. CAPOXIRI + BEV showed promising efficacy, including modified PFS defined based on TRIBE. Both treatments were well tolerated with no unexpected safety signals. According to efficacy and safety data regarding CAPOXIRI + BEV, it has potential as a new first-line treatment option for patients with mCRC.