Bevacizumab in Combination With Either FOLFOX-4 or XELOX-2 in First-line Treatment of Patients With Metastatic Colorectal Cancer: A Multicenter Randomized Phase II Trial of the Gruppo Oncologico dell’Italia Meridionale (GOIM 2802)

• Published in: Clinical colorectal cancer 2020-06, Vol.19 (2), p.109-115
• Main Authors: Maiello, Evaristo, Di Maggio, Gabriele, Cordio, Stefano, Cinieri, Saverio, Giuliani, Francesco, Pisconti, Salvatore, Rinaldi, Antonio, Febbraro, Antonio, Latiano, Tiziana Pia, Aieta, Michele, Rossi, Antonio, Rizzi, Daniele, Di Maio, Massimo, Colucci, Giuseppe, Bordonaro, Roberto
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Capecitabine; Capecitabine - administration & dosage; Capecitabine - adverse effects; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Elderly; Female; Fluoropyrimidine; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Frail; Humans; Leucovorin - administration & dosage; Leucovorin - adverse effects; Male; Middle Aged; Nausea - chemically induced; Nausea - diagnosis; Nausea - epidemiology; Neutropenia - chemically induced; Neutropenia - diagnosis; Neutropenia - epidemiology; Non-comparative; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Oxaloacetates - administration & dosage; Oxaloacetates - adverse effects; Progression-Free Survival; Severity of Illness Index
• ISSN: 1533-0028; 1938-0674
• DOI: 10.1016/j.clcc.2020.01.003

Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC. Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed. Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5. This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC. Bevacizumab plus either FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) or XELOX-2 (capecitabine plus oxaliplatin) is among standard first-line treatment options in patients with metastatic colorectal cancer. This phase II randomized non-comparative trial evaluated the first-line combination of bevacizumab with either FOLFOX-4 or biweekly XELOX-2 in patients with metastatic colorectal cancer. Comparable response and a better tolerability for bevacizumab plus XELOX-2 was reported.