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Clinical Trial
. 2025 Jul;43(19):2196-2207.
doi: 10.1200/JCO.24.01119. Epub 2025 May 23.

Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial

Daisuke Sakai  1   2 , Shigenori Kadowaki  3 , Ryohei Kawabata  4 , Hiroki Hara  5 , Hironaga Satake  6 , Masazumi Takahashi  7 , Atsushi Takeno  8 , Hiroo Imai  9 , Keiko Minashi  10 , Takeshi Kawakami  11 , Shogen Boku  12 , Jin Matsuyama  13 , Yasuhiro Sakamoto  14 , Kentaro Sawada  15 , Masato Kataoka  16 , Hisato Kawakami  9   17 , Toshio Shimokawa  18 , Narikazu Boku  19 , Taroh Satoh  2
Affiliations
Clinical Trial

Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial

Daisuke Sakai et al. J Clin Oncol. 2025 Jul.

Abstract

Purpose: 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.

Methods: 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.

Results: 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; P = .49). PFS was improved (median, 3.8 v 2.8 months; HR, 0.72 [95% CI, 0.59 to 0.89]; P = .002), while the DCR was significantly better (64.4% v 52.1%; P = .03) with the combination therapy. The adverse events of the combination therapy were manageable.

Conclusion: 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.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
CONSORT diagram of the study. ITT, intention-to-treat.
FIG 2.
FIG 2.
Kaplan-Meier curve of (A) OS and (B) PFS in patients with advanced gastric cancer receiving ramucirumab plus irinotecan or irinotecan monotherapy. OS, overall survival; PFS, progression-free survival.
FIG 3.
FIG 3.
Forest plot of (A) OS and (B) PFS in patients with advanced gastric cancer receiving ramucirumab plus irinotecan or irinotecan monotherapy. HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
FIG A1.
FIG A1.
Waterfall plot of (A) the ramucirumab plus irinotecan group and (B) the irinotecan monotherapy group.
FIG A2.
FIG A2.
Kaplan-Meier curves for (A) OS and (B) PFS in the intention-to-treat population. OS, overall survival; PFS, progression-free survival.
FIG A3.
FIG A3.
Kaplan-Meier curves for (A) OS and (B) PFS in the per-protocol set population. OS, overall survival; PFS, progression-free survival.
See this image and copyright information in PMC

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