Sakai Daisuke, Kadowaki Shigenori, Kawabata Ryohei, Hara Hiroki, Satake Hironaga, Takahashi Masazumi, Takeno Atsushi, Imai Hiroo, Minashi Keiko, Kawakami Takeshi, Boku Shogen, Matsuyama Jin, Sakamoto Yasuhiro, Sawada Kentaro, Kataoka Masato, Kawakami Hisato, Shimokawa Toshio, Boku Narikazu, Satoh Taroh
Osaka International Cancer Institute, Osaka, Japan.
Osaka University Hospital, Suita, Japan.
J Clin Oncol. 2025 Jul;43(19):2196-2207. doi: 10.1200/JCO.24.01119. Epub 2025 May 23.
Continuous use of antiangiogenic agents has demonstrated survival benefits in various cancers. This trial aimed to compare the efficacy and safety of ramucirumab plus irinotecan with irinotecan monotherapy as a third- or later-line treatment for patients with advanced or recurrent gastric or gastroesophageal cancer (AGC) that has progressed on previous ramucirumab-based chemotherapy.
Patients age 20 years and older with AGC, who had experienced disease progression during ramucirumab-based chemotherapy, were randomly assigned to receive either ramucirumab plus irinotecan or irinotecan monotherapy. The primary end point was overall survival (OS) expecting a hazard ratio (HR) of 0.77 (a power of 80% and a significance level of one-sided 0.05). Secondary end points included progression-free survival (PFS), response rate, disease control rate (DCR), and safety.
Between February 2017 and August 2022, 402 patients in Japan were randomly assigned to receive ramucirumab plus irinotecan (n = 202) or irinotecan monotherapy (n = 200). The median OS was 9.4 months in the combination arm and 8.5 months in the monotherapy arm, with an adjusted HR of 0.91 (95% CI, 0.74 to 1.12; = .49). PFS was improved (median, 3.8 2.8 months; HR, 0.72 [95% CI, 0.59 to 0.89]; = .002), while the DCR was significantly better (64.4% 52.1%; = .03) with the combination therapy. The adverse events of the combination therapy were manageable.
Adding ramucirumab to irinotecan does not provide a significant advantage in OS over irinotecan alone in patients with AGC who have progressed during ramucirumab-containing chemotherapy.
持续使用抗血管生成药物已在多种癌症中显示出生存获益。本试验旨在比较雷莫西尤单抗联合伊立替康与伊立替康单药治疗作为晚期或复发性胃癌或胃食管交界癌（AGC）三线及以上治疗的疗效和安全性，这些患者既往接受基于雷莫西尤单抗的化疗后病情进展。
年龄20岁及以上的AGC患者，在基于雷莫西尤单抗的化疗期间病情进展，被随机分配接受雷莫西尤单抗联合伊立替康或伊立替康单药治疗。主要终点是总生存期（OS），预期风险比（HR）为0.77（检验效能80%，单侧显著性水平0.05）。次要终点包括无进展生存期（PFS）、缓解率、疾病控制率（DCR）和安全性。
2017年2月至2022年8月期间，日本的402例患者被随机分配接受雷莫西尤单抗联合伊立替康（n = 202）或伊立替康单药治疗（n = 200）。联合治疗组的中位OS为9.4个月，单药治疗组为8.5个月，校正HR为0.91（95%CI，0.74至1.12；P = 0.49）。联合治疗改善了PFS（中位，3.8对2.8个月；HR，0.72[95%CI，0.59至0.89]；P = 0.002），同时联合治疗的DCR显著更好（64.4%对52.1%；P = 0.03）。联合治疗的不良事件可控。
对于在含雷莫西尤单抗化疗期间病情进展的AGC患者，在OS方面，伊立替康联合雷莫西尤单抗并不比单用伊立替康具有显著优势。
