Iihara Hirotoshi, Shimokawa Mototsugu, Bando Hiroko, Niwa Yoshimi, Mizuno Yutaka, Kawaguchi Yoshihiro, Kitahora Mika, Murakami Akari, Kawai Masaaki, Ishida Kazushige, Takeuchi Makoto, Ishihara Kazuhiro, Iyoda Tomokazu, Nakada Takumi, Ogiso Atsuko, Kojima Yasuyuki, Kumagai Fumiyoshi, Sawa Aya, Mori Ryutaro, Higuchi Kosuke, Furuta Tomoko, Kamei Yoshiaki, Tsuchiya Masami, Terasaki Azusa, Yamamoto Senri, Kitazawa Mai, Okazaki Mai, Suzuki Akio, Futamura Manabu
Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan.
Patient Safety Division, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan.
J Cancer. 2023 Aug 28;14(14):2644-2654. doi: 10.7150/jca.87169. eCollection 2023.
Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.
曲妥珠单抗德鲁替康在国际止吐治疗指南中被归类为具有中度致吐风险的抗癌药物。该指南推荐使用包含5-羟色胺-3受体拮抗剂（5-HT3RA）和地塞米松（DEX）的两药联合疗法进行呕吐预防。然而，与曲妥珠单抗德鲁替康相关的恶心和呕吐发生率较高，这是个问题。美国国立综合癌症网络2023年第1.2版指南将曲妥珠单抗德鲁替康归类为具有高呕吐风险，并将其推荐改为包括神经激肽-1受体拮抗剂（NK1RA）的三联方案。然而，曲妥珠单抗德鲁替康的致吐潜力和最佳止吐预防措施仍存在争议。因此，这项探索性2期研究旨在评估包含5-HT3RA和DEX（含或不含NK1RA）的治疗方案在预防曲妥珠单抗德鲁替康引起的恶心和呕吐方面的疗效和安全性。我们在日本的14个中心开展了一项开放标签的随机探索性2期研究。计划接受曲妥珠单抗德鲁替康治疗的乳腺癌患者被纳入本研究。患者被随机分配接受格拉司琼和DEX（GD组）或格拉司琼、DEX和阿瑞匹坦（福沙匹坦；GDA组）。主要终点是整个阶段（曲妥珠单抗德鲁替康开始给药后120小时）的完全缓解（CR；无呕吐或无需急救治疗）。在2020年9月至2023年3月期间，40例患者被随机分配至GD组（n = 19）或GDA组（n = 21）。在GDA组中，1例未完成日记中列出的急救药物使用的患者被排除在包括急救药物使用情况的疗效分析之外。GD组和GDA组在整个阶段的CR率分别为36.8%和70.0%（优势比0.1334；95%置信区间[CI]：0.0232 - 0.7672；P = 0.0190），差异为33.2%。未观察到与止吐治疗相关的3级或4级毒性反应。接受曲妥珠单抗德鲁替康治疗的患者需要三联疗法，包括必须使用NK-1RA。
