Abstract：
Current therapeutic regimens for patients with v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E-mutated colorectal cancer show unsatisfactory efficacy. To improve outcomes in this area, we assessed the safety and efficacy of a new protocol using vemurafenib and cetuximab combined with FOLFIRI (5-fluorouracil/leucovorin/irinotecan) in patients with BRAF V600E-mutated colorectal cancer.
This was an investigator-initiated, open-label, single-arm, phase II trial conducted in patients with BRAF V600E-mutated advanced colorectal cancer. Patients were eligible to receive FOLFIRI combined with vemurafenib and cetuximab. The primary end-point was the objective response rate, and the secondary end-points included disease control rate, progression-free survival, overall survival and safety. This trial is registered with ClinicalTrials.gov, NCT03727763.
Between 12th January 2018, and 18th June 2021, we screened 27 patients, 21 of which were enrolled in this study. Efficacy analysis showed that objective response rates were 81.0% (17/21; 95% confidence interval [CI] 57.4-93.7) in the intention-to-treat population and 85.0% (17/20, 95%CI 61.0-96.0) in the per-protocol population; two patients achieved complete response, and 15 patients achieved a partial response. In the entire cohort, the median progression-free survival was 9.7 months (95%CI 6.3-10.9), and the median overall survival for all patients was 15.4 months (95%CI 8.5-15.4). The most common adverse events (grade 3 to 4) were neutropenia (8/21), anaemia (3/21) and skin rash (3/21).
Vemurafenib and cetuximab can be safely combined with the FOLFIRI regimen, showing promising antitumour activity and tolerable toxicity in patients with BRAF V600E-mutated advanced colorectal cancer. This regimen warrants a further randomised study in phase III clinical trials.
This was an investigator-initiated, open-label, single-arm, phase II trial conducted in patients with BRAF V600E-mutated advanced colorectal cancer. Patients were eligible to receive FOLFIRI combined with vemurafenib and cetuximab. The primary end-point was the objective response rate, and the secondary end-points included disease control rate, progression-free survival, overall survival and safety. This trial is registered with ClinicalTrials.gov, NCT03727763.
Between 12th January 2018, and 18th June 2021, we screened 27 patients, 21 of which were enrolled in this study. Efficacy analysis showed that objective response rates were 81.0% (17/21; 95% confidence interval [CI] 57.4-93.7) in the intention-to-treat population and 85.0% (17/20, 95%CI 61.0-96.0) in the per-protocol population; two patients achieved complete response, and 15 patients achieved a partial response. In the entire cohort, the median progression-free survival was 9.7 months (95%CI 6.3-10.9), and the median overall survival for all patients was 15.4 months (95%CI 8.5-15.4). The most common adverse events (grade 3 to 4) were neutropenia (8/21), anaemia (3/21) and skin rash (3/21).
Vemurafenib and cetuximab can be safely combined with the FOLFIRI regimen, showing promising antitumour activity and tolerable toxicity in patients with BRAF V600E-mutated advanced colorectal cancer. This regimen warrants a further randomised study in phase III clinical trials.
摘要：
目前用于v-raf鼠肉瘤病毒癌基因同源物B1(BRAF)V600E突变的结直肠癌患者的治疗方案显示不令人满意的疗效。为了改善这方面的成果，在BRAFV600E突变结直肠癌患者中,我们评估了使用维罗非尼和西妥昔单抗联合FOLFIRI(5-氟尿嘧啶/亚叶酸钙/伊立替康)的新方案的安全性和有效性.
这是一个调查员发起的,开放标签，单臂,在BRAFV600E突变的晚期结直肠癌患者中进行的II期试验.患者有资格接受FOLFIRI联合vemurafenib和西妥昔单抗。主要终点是客观反应率，次要终点包括疾病控制率，无进展生存期,总体生存率和安全性。该试验已在ClinicalTrials.gov注册，NCT03727763。
在2018年1月12日至2021年6月18日之间，我们筛查了27名患者，其中21人参加了这项研究。疗效分析表明，意向治疗人群的客观缓解率为81.0%(17/21;95%置信区间[CI]57.4-93.7)，符合方案人群的客观缓解率为85.0%(17/20,95CI61.0-96.0)；两名患者达到完全缓解，15名患者获得部分缓解。在整个队列中，中位无进展生存期为9.7个月(95CI6.3-10.9),所有患者的中位总生存期为15.4个月(95CI8.5-15.4).最常见的不良事件（3至4级）是中性粒细胞减少症（8/21），贫血（3/21）和皮疹（3/21）。
维罗非尼和西妥昔单抗可以安全地与FOLFIRI方案联合使用，在BRAFV600E突变的晚期结直肠癌患者中显示出有希望的抗肿瘤活性和可耐受的毒性。该方案需要在III期临床试验中进行进一步的随机研究。
这是一个调查员发起的,开放标签，单臂,在BRAFV600E突变的晚期结直肠癌患者中进行的II期试验.患者有资格接受FOLFIRI联合vemurafenib和西妥昔单抗。主要终点是客观反应率，次要终点包括疾病控制率，无进展生存期,总体生存率和安全性。该试验已在ClinicalTrials.gov注册，NCT03727763。
在2018年1月12日至2021年6月18日之间，我们筛查了27名患者，其中21人参加了这项研究。疗效分析表明，意向治疗人群的客观缓解率为81.0%(17/21;95%置信区间[CI]57.4-93.7)，符合方案人群的客观缓解率为85.0%(17/20,95CI61.0-96.0)；两名患者达到完全缓解，15名患者获得部分缓解。在整个队列中，中位无进展生存期为9.7个月(95CI6.3-10.9),所有患者的中位总生存期为15.4个月(95CI8.5-15.4).最常见的不良事件（3至4级）是中性粒细胞减少症（8/21），贫血（3/21）和皮疹（3/21）。
维罗非尼和西妥昔单抗可以安全地与FOLFIRI方案联合使用，在BRAFV600E突变的晚期结直肠癌患者中显示出有希望的抗肿瘤活性和可耐受的毒性。该方案需要在III期临床试验中进行进一步的随机研究。
