恩考芬尼联合西妥昔单抗治疗BRAFV600E突变转移性结直肠癌患者的不良事件：BEACON CRC研究的深入分析
Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study.
作者信息
Taieb Julien, Lonardi Sara, Desai Jayesh, Folprecht Gunnar, Gallois Claire, Marques Eduardo Polo, Khan Sadya, Castagné Claire, Wasan Harpreet
机构信息
Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, AP-HP, Université Paris-Cité, SIRIC CARPEM, Paris University, Paris, France.
Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
出版信息
Clin Colorectal Cancer. 2023 Mar;22(1):59-66. doi: 10.1016/j.clcc.2022.12.003. Epub 2022 Dec 24.
BACKGROUND
The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAF-mutated (BRAFmut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAFmut mCRC patients who had progressed after 1-2 previous regimens. This analysis provides a detailed examination of the adverse events (AEs) of interest (AEIs) with encorafenib+cetuximab in the BEACON study to aid gastrointestinal oncologists, given the limited experience with this combination.
MATERIALS AND METHODS
AEIs, including dermatological AEs, arthralgia/myalgia, nausea/vomiting, diarrhea, abdominal pain, fatigue/asthenia and nephrotoxicity, were examined in the doublet therapy group. Clinical characteristics associated with these AEs, AE grade, time to onset and time to resolution were also studied.
RESULTS
Safety analysis included 216/220 patients randomized to doublet therapy. The most commonly occurring AEI was dermatological toxicity (75.5%), followed by arthralgia/myalgia (56.0%) and fatigue/asthenia (56.0%). Other than nephrotoxicity (7 patients; 5/7 with Grade 3 or 4), most AEs were Grade 1 or 2. Most AEs were more common in women than men (nausea/vomiting, diarrhea, abdominal pain, dermatological AEs, and arthralgia/myalgia). Nausea/vomiting, abdominal pain and fatigue/asthenia were more common in patients aged ≥70 years. Most AEs developed early, within the first 1-2 months of treatment, and resolved within 1-2 weeks. In addition, survival outcomes were better in patients experiencing arthralgia/myalgia or dermatological toxicities.
CONCLUSION
This analysis indicated that, except for rare cases of nephrotoxicity, encorafenib+cetuximab is well tolerated in most patients, with most AEIs being mild-to-moderate in severity, occurring early and resolving rapidly.
CLINICAL TRIAL REGISTRATION
the BEACON study (ClinicalTrials.gov, NCT02928224; EudraCT, 2015-005805-35).
背景
BRAF抑制剂恩考芬尼与西妥昔单抗联合用药最近被批准用于BRAF突变（BRAFmut）的转移性结直肠癌（mCRC）患者。该批准基于3期BEACON CRC研究的阳性结果，该研究针对的是在接受过1 - 2种先前治疗方案后病情进展的BRAFmut mCRC患者。鉴于这种联合用药的经验有限，本分析详细研究了BEACON研究中恩考芬尼+西妥昔单抗的感兴趣的不良事件（AEIs），以帮助胃肠肿瘤学家。
材料与方法
在双联治疗组中研究了AEIs，包括皮肤不良事件、关节痛/肌痛、恶心/呕吐、腹泻、腹痛、疲劳/乏力和肾毒性。还研究了与这些不良事件相关的临床特征、不良事件等级、发病时间和缓解时间。
结果
安全性分析纳入了220例随机接受双联治疗的患者中的216例。最常出现的AEI是皮肤毒性（75.5%），其次是关节痛/肌痛（56.0%）和疲劳/乏力（56.0%）。除肾毒性外（7例患者；5/7为3级或4级），大多数不良事件为1级或2级。大多数不良事件在女性中比男性更常见（恶心/呕吐、腹泻、腹痛、皮肤不良事件和关节痛/肌痛）。恶心/呕吐、腹痛和疲劳/乏力在年龄≥70岁的患者中更常见。大多数不良事件在治疗的前1 - 2个月内早期出现，并在1 - 2周内缓解。此外，出现关节痛/肌痛或皮肤毒性的患者生存结果更好。
结论
该分析表明，除了罕见的肾毒性病例外，大多数患者对恩考芬尼+西妥昔单抗耐受性良好，大多数AEIs严重程度为轻至中度，早期出现且迅速缓解。
临床试验注册
BEACON研究（ClinicalTrials.gov，NCT02928224；EudraCT，2015 - 005805 - 35）。
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