Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2023-03-01 DOI:10.1016/j.clcc.2022.12.003

Julien Taieb , Sara Lonardi , Jayesh Desai , Gunnar Folprecht , Claire Gallois , Eduardo Polo Marques , Sadya Khan , Claire Castagné , Harpreet Wasan

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引用次数: 2

Abstract

Background

The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAF^V600E-mutated (BRAF^V600Emut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAF^V600Emut 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)

查看原文本刊更多论文

BRAFV600E突变型转移性结直肠癌癌症患者与安可非尼加西妥昔单抗相关的不良事件：对BEACON CRC研究的深入分析

背景BRAF抑制剂安可非尼联合西妥昔单抗最近被批准用于BRAFV600E突变（BRAFV600Emut）转移性癌症（mCRC）患者。批准是基于对BRAFV600Emut mCRC患者进行的3期BEACON CRC研究的阳性结果，这些患者在之前的1-2个方案后取得了进展。鉴于这种组合的经验有限，该分析提供了对BEACON研究中安克拉芬尼+西妥昔单抗的不良事件（AE）的详细检查，以帮助胃肠道肿瘤学家。材料和方法双重治疗组检查AE，包括皮肤科AE、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AE相关的临床特征、AE分级、发病时间和消退时间。结果安全性分析包括216/220名随机接受双重治疗的患者。最常见的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%。大多数AE在女性中比男性更常见（恶心/呕吐、腹泻、腹痛、皮肤病AE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AE在治疗的前1-2个月内早期出现，并在1-2周内解决。此外，经历关节痛/肌痛或皮肤毒性的患者的生存结果更好。结论该分析表明，除了罕见的肾毒性病例外，安克拉芬尼+西妥昔单抗在大多数患者中耐受性良好，大多数不良事件的严重程度为轻度至中度，发生时间早，解决速度快。临床试验注册BEACON研究（ClinicalTrials.gov，NCT02928224；EudraCT，2015-005805-35）

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来源期刊

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.