論文

査読有り 国際誌
2020年6月20日

Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603).

Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • Shota Fukuoka
  • Hiroki Hara
  • Naoki Takahashi
  • Takashi Kojima
  • Akihito Kawazoe
  • Masako Asayama
  • Takako Yoshii
  • Daisuke Kotani
  • Hitomi Tamura
  • Yuichi Mikamoto
  • Nami Hirano
  • Masashi Wakabayashi
  • Shogo Nomura
  • Akihiro Sato
  • Takeshi Kuwata
  • Yosuke Togashi
  • Hiroyoshi Nishikawa
  • Kohei Shitara
  • 全て表示

38
18
開始ページ
2053
終了ページ
2061
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1200/JCO.19.03296

PURPOSE: This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer. PATIENTS AND METHODS: Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose. RESULTS: Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received ≥ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability-high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair-proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade ≥ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively. CONCLUSION: The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.

リンク情報
DOI
https://doi.org/10.1200/JCO.19.03296
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32343640
ID情報
  • DOI : 10.1200/JCO.19.03296
  • PubMed ID : 32343640

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