P-80 A multicenter randomized phase II study comparing CAPOXIRI plus bevacizumab and FOLFOXIRI plus bevacizumab as the first-line treatment for metastatic colorectal cancer: A safety analysis of the QUATTRO-II study

Abstract

FOLFOXIRI plus bevacizumab (BEV) is the standard first-line treatment for metastatic colorectal cancer (mCRC) despite its association with a high incidence of neutropenia and diarrhea. In this study, capecitabine (CAP), oxaliplatin (OX), and irinotecan (IRI) (CAPOXIRI) plus BEV are hypothesized to be more feasible than FOLFOXIRI plus BEV, without compromising the efficacy. Here, results of safety analysis in the induction phase are reported in the randomized phase II QUATTRO-II study comparing CAPOXIRI plus BEV and FOLFOXIRI plus BEV as the first-line treatment for mCRC. This multicenter, open-label, randomized phase II study enrolled patients with the ECOG performance status of 0 or 1, without previous chemotherapy in the metastatic setting, with adequate organ function, and with UGT1A1 *6/*28 gene polymorphisms of wild-type or single heterozygous. Patients were randomized in a 1:1 ratio to FOLFOXIRI plus BEV (arm A) or CAPOXIRI plus BEV (arm B). As we previously reported, the recommended phase II doses of CAPOXIRI plus BEV were determined as CAP, 1,600 mg/m2; OX, 130 mg/m2; IRI, 200 mg/m2; and BEV, 7.5 mg/kg every 3 weeks from the results of Safety Lead-In of this study. FOLFOXIRI plus BEV or CAPOXIRI plus BEV in the induction phase was continued until 8/6 (arm A/B) cycles (maximum, 12/8 cycles), followed by 5-FU/l-LV plus BEV or CAP plus BEV in the maintenance phase at the investigator’s discretion. The primary endpoint was progression-free survival, and secondary endpoints were overall response rate, overall survival, and safety. The completion of the induction phase was defined as meeting both of the following two criteria in all cycles: all drugs are administered (dose reduction was permitted); and the cycle was started within 28 days of the planned start date. A total of 103 patients (arm A/B, 51/52) were enrolled from June 2020 to June 2021. Baseline patient characteristics (arm A/B), including the median age (range), 60 (38–75)/60 (35–77) years; the ECOG performance status of 0, 46 (90%)/49 (94%); and UGT1A1 *6/*28 gene polymorphisms, wild-type 30 (59%)/29 (56%) were similar between the two treatment arms. At the data cutoff of December 17, 2021, the incidence of grade >3 major adverse events (AEs) in the induction phase was as follows (arm A/B): neutropenia (65%/39%), febrile neutropenia (10%/12%), diarrhea (8%/17%), and anorexia (8%/17%). No treatment-related deaths occurred. Among patients in arms A and B, 26 (51%) and 30 (58%) patients achieved the completion of the induction phase, respectively. The main reasons for incompletion of the induction phase (arm A/B) were treatment discontinuation due to resection (9/9), disease progression (2/5), and adverse events (5/1) and not meeting the definition of completion of the induction phase (6/6). This safety analysis showed that both CAPOXIRI plus BEV and FOLFOXIRI plus BEV were safe and tolerable with differences in AE incidences and toxicity profiles. The QUATTRO-II study is still in the follow-up phase, and the efficacy data will be reported in next year’s scientific meeting.