Department of Pharmacovigilance, Ono Pharmaceutical, Co., Ltd., 1-5, Dosho-Machi 2-Chome, Chuo-Ku, Osaka, 541-8526, Japan.
Department of Oncology Medical Affairs, Ono Pharmaceutical, Co., Ltd., 3-8-20, Marunouchi, Naka-Ku, Nagoya, Aichi, 460-0002, Japan.
Int J Clin Oncol. 2023 Jan;28(1):139-144. doi: 10.1007/s10147-022-02264-z. Epub 2022 Nov 10.
Triplet and doublet regimens of encorafenib plus cetuximab with and without binimetinib, respectively, were approved in Japan for unresectable, metastatic, BRAF V600E-mutated colorectal cancer (mCRC) that had progressed after 1-2 prior chemotherapies. This early post-marketing phase vigilance (EPPV) study collected adverse drug reactions (ADRs) from Japanese patients to ensure safety measures as appropriate.
Patients with BRAF V600E mCRC who received the triplet or doublet regimens in Japan were selected for this study. ADRs were collected as spontaneous reports between November 27, 2020 and May 26, 2021. Serious ADRs were evaluated according to guidelines of the International Council for Harmonisation and the EudraVigilance list of Important Medical Event Terms.
An estimated 550 Japanese patients with mCRC received the triplet or doublet regimens during the 6-month EPPV period. Overall, 101 and 42 patients reported ADRs and serious ADRs, respectively. No ADRs leading to death were reported. The most frequently reported ADRs were nausea (17 patients), serous retinal detachment (16), decreased appetite (12), diarrhea (11), and vomiting (11). Among the important identified/potential risks that are defined in the risk management plans for encorafenib and binimetinib, eye disorder-related ADRs were observed in 32 patients, rhabdomyolysis-related ADRs in 12, hemorrhage-related ADRs in 7, and hepatic dysfunction-related ADRs in 7. Of 22 patients with serious eye disorders, 20 recovered or were recovering during the EPPV period.
The safety profile in this EPPV study was similar to that from the phase III BEACON CRC study and no new safety concerns were identified.
依维莫司、西妥昔单抗分别与恩考芬尼三联和二联方案获批用于既往接受过 1-2 线化疗后进展的不可切除、转移性、BRAF V600E 突变结直肠癌（mCRC），在日本。本项上市后早期警戒（EPPV）研究收集了日本患者的药物不良反应（ADR）数据，以确保采取适当的安全措施。
选择在日本接受依维莫司、西妥昔单抗三联和二联方案治疗的 BRAF V600E mCRC 患者进行本项研究。ADR 数据为 2020 年 11 月 27 日至 2021 年 5 月 26 日期间自发报告。严重 ADR 根据国际协调会议和 EudraVigilance 重要医学事件术语清单的指南进行评估。
在 6 个月的 EPPV 期间，估计有 550 例 mCRC 日本患者接受了三联或二联方案治疗。共有 101 例和 42 例患者报告了 ADR 和严重 ADR。未报告导致死亡的 ADR。最常见的 ADR 为恶心（17 例）、浆液性视网膜脱离（16 例）、食欲下降（12 例）、腹泻（11 例）和呕吐（11 例）。在依维莫司和 binimetinib 的风险管理计划中定义的重要已识别/潜在风险中，观察到 32 例患者出现眼部疾病相关 ADR、12 例患者出现横纹肌溶解相关 ADR、7 例患者出现出血相关 ADR 和 7 例患者出现肝功能障碍相关 ADR。在 22 例严重眼部疾病患者中，20 例在 EPPV 期间恢复或正在恢复。
本 EPPV 研究的安全性与 III 期 BEACON CRC 研究相似，未发现新的安全性问题。
