Georgetown Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA.
Center for Immuno-Oncology Research, Cleveland Clinic, Cleveland, OH 44106, USA.
Immunotherapy. 2019 May;11(7):617-629. doi: 10.2217/imt-2018-0208. Epub 2019 Mar 11.
Comparison of clinical outcomes of nivolumab + ipilimumab versus BRAF + MEK inhibitors (dabrafenib + trametinib or vemurafenib + cobimetinib) in BRAF-mutant advanced melanoma.
Matching-adjusted indirect comparisons were conducted between nivolumab + ipilimumab (CheckMate 067/069 studies) and BRAF + MEK inhibitors (COMBI-d, COMBI-v and coBRIM studies). Overall survival (OS), progression-free survival and objective response rates were assessed.
After adjusting, nivolumab + ipilimumab showed improved OS versus dabrafenib + trametinib (hazard ratio [HR] = 0.64; 95% CI: 0.46-0.89) or vemurafenib + cobimetinib (HR = 0.56; 95% CI: 0.36-0.89); OS outcomes were similar at 1 year, with benefits emerging after 12 months; progression-free survival and objective response rates were similar. Grade 3/4 adverse events occurred in 54.1% with nivolumab + ipilimumab, 31.6% with dabrafenib + trametinib and 59.5% with vemurafenib + cobimetinib.
Nivolumab + ipilimumab had significantly improved clinical outcomes versus BRAF + MEK inhibitors, with benefits increasing after longer follow-up. Ongoing randomized trials directly comparing these treatments are necessary to prospectively validate these findings.
比较纳武单抗+伊匹单抗与 BRAF+MEK 抑制剂（达拉非尼+曲美替尼或维莫非尼+考比替尼）治疗 BRAF 突变型晚期黑色素瘤的临床结局。
在纳武单抗+伊匹单抗（CheckMate 067/069 研究）和 BRAF+MEK 抑制剂（COMBI-d、COMBI-v 和 coBRIM 研究）之间进行了匹配调整间接比较。评估总生存期（OS）、无进展生存期和客观缓解率。
调整后，纳武单抗+伊匹单抗与达拉非尼+曲美替尼（风险比 [HR] = 0.64；95%置信区间：0.46-0.89）或维莫非尼+考比替尼（HR = 0.56；95%置信区间：0.36-0.89）相比，OS 得到改善；1 年时 OS 结果相似，12 个月后出现获益；无进展生存期和客观缓解率相似。纳武单抗+伊匹单抗组发生 3/4 级不良事件 54.1%，达拉非尼+曲美替尼组为 31.6%，维莫非尼+考比替尼组为 59.5%。
纳武单抗+伊匹单抗与 BRAF+MEK 抑制剂相比，临床结局显著改善，随访时间延长后获益增加。有必要开展直接比较这些治疗方法的随机临床试验，以前瞻性验证这些发现。
