Inada Ryo, Nagasaka Takeshi, Shimokawa Mototsugu, Ojima Hitoshi, Noura Shingo, Tanioka Hiroaki, Munemoto Yoshinori, Shimada Yasuhiro, Ishibashi Keiichiro, Shindo Yoshiaki, Mishima Hideyuki, Okajima Masasumi, Yamaguchi Yoshiyuki
Department of Gastroenterological Surgery, Kochi Health Sciences Centre, Kochi, Kochi, Japan; Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
Department of Clinical Oncology, Kawasaki Medical School Hospital, Kurashiki, Okayama, Japan; Department of Gastroenterological Surgery, Okayama University Hospital, Okayama, Okayama, Japan.
Eur J Cancer. 2022 Jul;169:166-178. doi: 10.1016/j.ejca.2022.04.009. Epub 2022 May 13.
An optimal treatment strategy using oxaliplatin and bevacizumab for metastatic colorectal cancer has not been defined. We investigated whether the sequential treatment using fluoropyrimidines with bevacizumab followed by the addition of oxaliplatin at first progression was better than a combination treatment using fluoropyrimidines and oxaliplatin with bevacizumab.
In the sequential treatment, the escalation from fluoropyrimidines plus bevacizumab to fluoropyrimidines plus oxaliplatin with bevacizumab was recommended in case of progressive disease. Time to failure of strategy was the primary end-point, whereas the secondary end-points were overall survival, progression-free survival, overall response rate and safety.
Three hundred patients with previously untreated metastatic colorectal cancer were randomised to receive either the sequential treatment (n = 151) or the combination treatment (n = 149). The sequential treatment was superior to the combination treatment about time to failure of strategy (15.2 months; 95% CI, 12.5-17.2 months vs. 7.8 months: 95% CI, 6.3-9.5 months; P < 0.001). However, the median overall survival was 27.5 (95% CI, 24.4 to 32.7) months in the sequential treatment and 27.0 (95% CI, 22.8 to 36.0) months in the combination treatment (hazard ratio, 0.92; 95% CI, 0.66 to 1.28; P = 0.61). The overall response rate was 33.1% in the sequential treatment arm and 51.7% in the combination treatment.
The findings support the extension of the sequential treatment starting from fluoropyrimidine plus bevacizumab to selected patients who do not need an objective response to the threatening disease.
使用奥沙利铂和贝伐单抗治疗转移性结直肠癌的最佳治疗策略尚未明确。我们研究了在一线治疗中使用氟嘧啶联合贝伐单抗，在疾病首次进展时加用奥沙利铂的序贯治疗方案是否优于氟嘧啶、奥沙利铂联合贝伐单抗的联合治疗方案。
在序贯治疗中，若疾病进展，建议从氟嘧啶加贝伐单抗逐步升级为氟嘧啶加奥沙利铂联合贝伐单抗。治疗策略失败时间是主要终点，而次要终点包括总生存期、无进展生存期、总缓解率和安全性。
300例既往未接受治疗的转移性结直肠癌患者被随机分为序贯治疗组（n = 151）或联合治疗组（n = 149）。序贯治疗在治疗策略失败时间方面优于联合治疗（15.2个月；95%可信区间，12.5 - 17.2个月 vs. 7.8个月：95%可信区间，6.3 - 9.5个月；P < 0.001）。然而，序贯治疗组的中位总生存期为27.5（95%可信区间，24.4至32.7）个月，联合治疗组为27.0（95%可信区间，22.8至36.0）个月（风险比，0.92；95%可信区间，0.66至1.28；P = 0.61）。序贯治疗组的总缓解率为33.1%，联合治疗组为51.7%。
研究结果支持将从氟嘧啶加贝伐单抗开始的序贯治疗扩展至对威胁性疾病无需客观缓解的特定患者。
