文章：

COMBI-r：一项针对未经筛选的不可切除或转移性BRAF V600突变黑色素瘤患者使用达拉非尼联合曲美替尼的前瞻性、非干预性研究

COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma

原文发布日期：6 September 2023

DOI: 10.3390/cancers15184436

类型: Article

开放获取: 是

英文摘要：

Combined BRAF/MEK-inhibition constitutes a relevant treatment option forBRAF-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials.

摘要翻译： 

联合BRAF/MEK抑制剂治疗是BRAF突变晚期黑色素瘤的重要治疗选择。前瞻性、非干预性COMBI-r研究评估了BRAF抑制剂达拉非尼联合MEK抑制剂曲美替尼在常规临床条件下治疗晚期黑色素瘤患者的有效性和耐受性。研究主要终点为无进展生存期（PFS），次要终点包括总生存期（OS）、疾病控制率、治疗持续时间以及不良事件发生频率与严重程度。该研究在德国55个中心共纳入472例患者。中位PFS为8.3个月（95%CI 7.1–9.3），中位OS为18.3个月（14.9–21.3），且经治患者的两项指标均呈现延长趋势。在147例中枢神经系统转移患者中，需使用皮质类固醇组（可能代表有症状患者）与无需使用组PFS相近（分别为5.6个月（3.9–7.2）和5.9个月（4.8–6.9））；但脑转移患者中接受皮质类固醇治疗者的OS（7.8个月（6.3–11.6））较未接受者（11.9个月（9.6–19.5））更短。肿瘤生长动态的综合主观评估被证实有助于预测结局：研究者的事前分类与事件发生时间结局具有良好相关性。总体而言，COMBI-r研究反映了其他前瞻性观察性研究的PFS结果，并证实了关键III期COMBI-d/-v和COMBI-mb试验的疗效与安全性结论。

原文链接：

COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma