Department of Gastroenterology, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan.
Division of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
Int J Cancer. 2024 Dec 15;155(12):2223-2231. doi: 10.1002/ijc.35116. Epub 2024 Aug 14.
Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m, leucovorin 200 mg/m iv, bolus 5-fluorouracil [5-FU] 400 mg/m, and infusional 5-FU 2400 mg/m/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6-month PFS rate was 58.8% (90% confidence interval [CI], 45.7%-72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5-11.0 months) and 18.8 months (95% CI, 12.9-26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0-36.0%) and disease control rate was 88.4% (95% CI, 74.9-96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.
阿柏西普（AFL）联合 FOLFIRI 延长了转移性结直肠癌（mCRC）患者的总生存期（OS）。然而，此前接受过抗表皮生长因子受体（EGFR）治疗的 mCRC 患者使用 AFL 联合 FOLFIRI 的疗效和安全性证据有限。因此，我们开展了一项前瞻性、开放标签的 II 期临床试验，评估 AFL 联合 FOLFIRI 在既往接受奥沙利铂为基础的化疗加抗 EGFR 治疗失败的日本 mCRC 患者中的疗效和安全性。AFL（4mg/kg，静脉注射）继以 FOLFIRI（伊立替康 180mg/m2、亚叶酸钙 200mg/m2，静脉推注 5-氟尿嘧啶 [5-FU] 400mg/m2，5-FU 持续输注 2400mg/m2/46h），每 2 周 1 次，直至疾病进展或出现不可耐受的毒性。主要终点为 6 个月时的无进展生存期（PFS）率。2019 年 11 月至 2022 年 10 月期间共入组 43 例患者。主要终点达成：6 个月 PFS 率为 58.8%（90%可信区间，45.7%-72.0%）。中位 PFS 和 OS 分别为 7.3 个月（95%可信区间，5.5-11.0 个月）和 18.8 个月（95%可信区间，12.9-26.6 个月）。总缓解率为 20.9%（95%可信区间，10.0%-36.0%），疾病控制率为 88.4%（95%可信区间，74.9%-96.1%）。主要的 3 级及以上不良事件包括高血压（62.8%）、中性粒细胞减少（55.8%）、白细胞减少（25.6%）、发热性中性粒细胞减少（11.6%）、疲劳（9.3%）、食欲下降（9.3%）、蛋白尿（9.3%）和腹泻（7.0%）。未观察到死亡和与研究治疗有因果关系的新的安全性信号。本研究提示，AFL 联合 FOLFIRI 对既往奥沙利铂为基础的化疗加抗 EGFR 治疗失败的日本 mCRC 患者具有较高的缓解率和可管理的安全性。
