Julien Taieb , Sara Lonardi , Jayesh Desai , Gunnar Folprecht , Claire Gallois , Eduardo Polo Marques , Sadya Khan , Claire Castagné , Harpreet Wasan
{"title":"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","authors":"Julien Taieb , Sara Lonardi , Jayesh Desai , Gunnar Folprecht , Claire Gallois , Eduardo Polo Marques , Sadya Khan , Claire Castagné , Harpreet Wasan","doi":"10.1016/j.clcc.2022.12.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with <em>BRAF</em><sup>V600E</sup>-mutated (<em>BRAF</em><sup>V600E</sup>mut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in <em>BRAF</em><sup>V600E</sup>mut 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.</p></div><div><h3>Materials and Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div><div><h3>Clinical Trial Registration</h3><p>the BEACON study (ClinicalTrials.gov, NCT02928224; EudraCT, 2015-005805-35)</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study\",\"authors\":\"Julien Taieb , Sara Lonardi , Jayesh Desai , Gunnar Folprecht , Claire Gallois , Eduardo Polo Marques , Sadya Khan , Claire Castagné , Harpreet Wasan\",\"doi\":\"10.1016/j.clcc.2022.12.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with <em>BRAF</em><sup>V600E</sup>-mutated (<em>BRAF</em><sup>V600E</sup>mut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in <em>BRAF</em><sup>V600E</sup>mut 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.</p></div><div><h3>Materials and Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div><div><h3>Clinical Trial Registration</h3><p>the BEACON study (ClinicalTrials.gov, NCT02928224; EudraCT, 2015-005805-35)</p></div>\",\"PeriodicalId\":10373,\"journal\":{\"name\":\"Clinical colorectal cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical colorectal cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1533002822001347\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical colorectal cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1533002822001347","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study
Background
The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAFV600E-mutated (BRAFV600Emut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAFV600Emut 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)
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
