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

Author(s): Daisuke Sakai, MD^1,2; Shigenori Kadowaki, MD, PhD³; Ryohei Kawabata, MD, PhD⁴; Hiroki Hara, MD⁵; Hironaga Satake, MD, PhD⁶; Masazumi Takahashi, MD, PhD⁷; Atsushi Takeno, MD, PhD⁸; Hiroo Imai, MD, PhD⁹; Keiko Minashi, MD¹⁰; Takeshi Kawakami, MD, PhD¹¹; Shogen Boku, MD, PhD¹²; Jin Matsuyama, MD, PhD¹³; Yasuhiro Sakamoto, MD, PhD¹⁴; Kentaro Sawada, MD, PhD¹⁵; Masato Kataoka, MD, PhD¹⁶; Hisato Kawakami, MD, PhD^9,17; Toshio Shimokawa, PhD¹⁸; Narikazu Boku, MD, PhD¹⁹; Taroh Satoh, MD, PhD²;

Source: DOI:10.1200/JCO.24.01119

Dr. Anjan Patel's Thoughts

The RINDBeRG phase III trial investigated Ram + IRI versus IRI alone in Ram-refractory advanced gastric cancer, showing a significant improvement in progression-free survival (PFS) (3.8 vs 2.8 months) but no significant difference in overall survival (OS) (9.4 vs 8.5 months). The combination therapy achieved a higher overall response rate (ORR) (22.1% vs 15.0%) and disease control rate (DCR) (64.4% vs 52.1%), indicating likely modest antitumor activity. This combo offers a slight edge in delaying progression, but the lack of overall survival (OS) benefit means we’ll need to carefully consider its role in practice.

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.

Author Affiliations

¹Osaka International Cancer Institute, Osaka, Japan; ²Osaka University Hospital, Suita, Japan; ³Aichi Cancer Center Hospital, Nagoya, Japan; ⁴Osaka Rosai Hospital, Sakai, Japan; ⁵Saitama Cancer Center, Ina, Japan; ⁶Kobe City Medical Center General Hospital, Kobe, Japan; ⁷Yokohama Municipal Citizen’s Hospital, Yokohama, Japan; ⁸National Hospital Organization Osaka National Hospital, Osaka, Japan; ⁹Tohoku University Hospital, Sendai, Japan; ¹⁰Chiba Cancer Center, Chiba, Japan; ¹¹Shizuoka Cancer Center, Sunto-gun, Japan; ¹²Kansai Medical University Hospital, Hirakata, Japan; ¹³Higashiosaka City Medical Center, Higashi-Osaka, Japan; ¹⁴Osaki Citizen Hospital, Osaki, Japan; ¹⁵Kushiro Rosai Hospital, Kushiro, Japan; ¹⁶National Hospital Organization Nagoya Medical Center, Nagoya, Japan; ¹⁷Kindai University Faculty of Medicine, Osaka-Sayama, Japan; ¹⁸Wakayama Medical University, Wakayama, Japan; ¹⁹IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan;

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