Oxaliplatin Added to Fluoropyrimidine/Bevacizumab as Initial Therapy for Unresectable Metastatic Colorectal Cancer in Older Patients: A Multicenter, Randomized, Open-Label Phase III Trial (JCOG1018)

Author(s): Atsuo Takashima, MD¹; Tetsuya Hamaguchi, MD²; Junki Mizusawa, PhD³; Fumio Nagashima, MD⁴; Masahiko Ando, MD⁵; Hitoshi Ojima, MD⁶; Tadamichi Denda, MD⁷; Jun Watanabe, MD⁸; Katsunori Shinozaki, MD⁹; Hideo Baba, MD¹⁰; Masako Asayama, MD¹¹; Seiji Hasegawa, MD¹²; Toshiki Masuishi, MD¹³; Ken Nakata, MD¹⁴; Shunsuke Tsukamoto, MD¹⁵; Hiroshi Katayama, MD³; Kenichi Nakamura, MD³; Haruhiko Fukud, MD³; Yukihide Kanemitsu, MD¹⁵; Yasuhiro Shimada, MD¹⁶

Source: https://doi.org/10.1200/JCO.23.02722

Dr. Anjan Patel's Thoughts

This Japanese study showed no benefit with the addition of oxaliplatin to fluoropyrimidine plus bevacizumab (5FU+bev) in patients who were aged 70-74 but unfit, or >=75. Interestingly survival was actually shorter in the patients who received oxaliplatin at 21.3 vs 19.7 months.

PURPOSE

Doublet chemotherapy with fluoropyrimidine (FP) and oxaliplatin (OX) plus bevacizumab (BEV) is a standard regimen for unresectable metastatic colorectal cancer (MCRC). However, the efficacy of adding OX to FP plus BEV (FP + BEV) remains unclear for older patients, a population for whom FP + BEV is standard. We aimed to confirm the superiority of adding OX to FP + BEV for this population.

METHODS

This open-label, randomized, phase III trial was conducted at 42 institutions in Japan. Patients with unresectable MCRC age 70-74 years with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 and those 75 years and older with ECOG-PS 0-2 were randomly assigned (1:1) to an FP + BEV arm or an OX addition (FP + BEV + OX) arm. Fluorouracil plus levofolinate calcium or capecitabine was declared before enrollment. The primary end point was progression-free survival (PFS). The study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031180145).

RESULTS

Between September 2012 and March 2019, 251 patients were randomly assigned to the FP + BEV arm (n = 125) and the FP + BEV + OX arm (n = 126). The median age was 80 and 79 years in the respective arm. The median PFS was 9.4 months (95% CI, 8.3 to 10.3) in the FP + BEV arm and 10.0 months (9.0 to 11.2) in the FP + BEV + OX arm (hazard ratio [HR], 0.84 [90.5% CI, 0.67 to 1.04]; one-sided P = .086). The median overall survival was 21.3 months (18.7 to 24.3) in the FP + BEV arm and 19.7 months (15.5 to 25.5) in the FP + BEV + OX arm (HR, 1.05 [0.81 to 1.37]). The proportion of any grade ≥3 adverse events was higher in the FP + BEV + OX arm (52% v 69%). There was one treatment-related death in the FP + BEV arm and three in the FP + BEV + OX arm.

CONCLUSION

No benefit of adding OX to FP + BEV as first-line treatment was demonstrated in older patients with MCRC. FP + BEV is recommended for this population.

Author Affiliations

¹Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan; ²Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan; ³JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan; ⁴Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan; ⁵Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; ⁶Department of Gastroenterological Surgery, Gunma Prefectural Cancer Center, Gunma, Japan; ⁷Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan; ⁸Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; ⁹Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan; ¹⁰Department of Gastroenterology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; ¹¹Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan; ¹²Department of Clinical Oncology, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan; ¹³Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; ¹⁴Department of Colorectal Surgery, Sakai City Medical Center, Osaka, Japan; ¹⁵Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan; ¹⁶Department of Clinical Oncology, Kochi Health Sciences Center, Kochi, Japan

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