阿柏西普 (AFL) 联合 FOLFIRI 可延长转移性结直肠癌 (mCRC) 患者的总生存期 (OS)。然而，关于 AFL 联合先前使用抗表皮生长因子受体 (EGFR) 药物治疗的 FOLFIRI 的有效性和安全性的证据有限。因此，我们进行了一项前瞻性开放标签 II 期试验，评估 AFL 联合 FOLFIRI 对既往基于奥沙利铂的化疗加抗 EGFR 药物失败的日本 mCRC 患者的疗效和安全性。 AFL（4mg/kg 静脉注射），然后是 FOLFIRI（伊立替康 180mg/m2、亚叶酸 200mg/m2 静脉注射、推注 5-氟尿嘧啶 [5-FU] 400mg/m2 和输注 5-FU 2400mg/m2/46 h) 每两周给药一次，直至出现进展或出现不可接受的毒性。主要终点是 6 个月时的无进展生存率 (PFS)。 2019 年 11 月至 2022 年 10 月期间入组了 43 名患者。达到了主要终点：6 个月 PFS 率为 58.8%（90% 置信区间 [CI]，45.7%-72.0%）。中位 PFS 和 OS 分别为 7.3 个月（95% CI，5.5-11.0 个月）和 18.8 个月（95% CI，12.9-26.6 个月）。总体缓解率为 20.9%（95% CI，10.0-36.0%），疾病控制率为 88.4%（95% CI，74.9-96.1%）。主要≥3级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%）、厌食（9.3%）、蛋白尿（9.3%）和腹泻（7.0%）。没有观察到死亡，也没有观察到与研究治疗有因果关系的新安全信号。这项研究表明，AFL 联合 FOLFIRI 对既往基于奥沙利铂的化疗加抗 EGFR 药物失败的日本转移性结直肠癌患者显示出较高的缓解率和可控的安全性。© 2024 作者。约翰·威利出版的《国际癌症杂志》

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/m2, leucovorin 200 mg/m2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 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.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.