Haut-Tumor-Zentrum Hannover, Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover, Hannover, Germany.
Moscow City Oncology Hospital Number 62 of Moscow Healthcare Department, Moscow, Russia.
Lancet. 2020 Jun 13;395(10240):1835-1844. doi: 10.1016/S0140-6736(20)30934-X.
IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAF mutation-positive advanced or metastatic melanoma.
IMspire150 was a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAF mutation-positive melanoma were randomly assigned 1:1 to 28-day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo, vemurafenib, and cobimetinib (control group). In cycle 1, all patients received vemurafenib and cobimetinib only; atezolizumab placebo was added from cycle 2 onward. Randomisation was stratified by lactate dehydrogenase concentration and geographical region. Blinding for atezolizumab was achieved by means of an identical intravenous placebo, and blinding for vemurafenib was achieved by means of a placebo tablet. The primary outcome was investigator-assessed progression-free survival. This trial (ClinicalTrials.gov, NCT02908672) is ongoing but no longer recruiting patients.
Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and randomly assigned to the atezolizumab group (n=256) or control group (n=258). At a median follow-up of 18·9 months (IQR 10·4-23·8), progression-free survival as assessed by the study investigator was significantly prolonged with atezolizumab versus control (15·1 vs 10·6 months; hazard ratio [HR] 0·78; 95% CI 0·63-0·97; p=0·025). Common treatment-related adverse events (>30%) in the atezolizumab and control groups were blood creatinine phosphokinase increased (51·3% vs 44·8%), diarrhoea (42·2% vs 46·6%), rash (40·9%, both groups), arthralgia (39·1% vs 28·1%), pyrexia (38·7% vs 26·0%), alanine aminotransferase increased (33·9% vs 22·8%), and lipase increased (32·2% vs 27·4%); 13% of patients in the atezolizumab group and 16% in the control group stopped all treatment because of adverse events.
The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAF mutation-positive advanced melanoma.
F Hoffmann-La Roche and Genentech.
IMspire150 旨在评估 BRAF 突变阳性的晚期或转移性黑色素瘤的一线联合治疗，包括 BRAF 加 MEK 抑制剂和免疫检查点治疗。
IMspire150 是一项在 20 个国家的 112 个机构进行的随机、双盲、安慰剂对照的 3 期研究。不可切除的 IIIc-IV 期、BRAF 突变阳性黑色素瘤患者按 1:1 随机分配至 28 天周期的阿替利珠单抗、维莫非尼和考比替尼（阿替利珠单抗组）或阿替利珠单抗安慰剂、维莫非尼和考比替尼（对照组）。在第 1 周期，所有患者仅接受维莫非尼和考比替尼治疗；从第 2 周期开始，加入阿替利珠单抗安慰剂。随机分组按乳酸脱氢酶浓度和地理区域分层。通过给予阿替利珠单抗相同的静脉内安慰剂来实现阿替利珠单抗的盲法，通过给予维莫非尼安慰剂片来实现维莫非尼的盲法。主要终点是研究者评估的无进展生存期。该试验（ClinicalTrials.gov，NCT02908672）正在进行中，但不再招募患者。
2017 年 1 月 13 日至 2018 年 4 月 26 日，筛选了 777 例患者，入组了 514 例并随机分配至阿替利珠单抗组（n=256）或对照组（n=258）。在中位随访 18.9 个月（IQR 10.4-23.8）时，研究研究者评估的无进展生存期阿替利珠单抗组明显长于对照组（15.1 个月 vs 10.6 个月；风险比[HR]0.78；95%CI 0.63-0.97；p=0.025）。阿替利珠单抗组和对照组中常见的治疗相关不良事件（发生率>30%）包括血肌酸磷酸激酶升高（51.3% vs 44.8%）、腹泻（42.2% vs 46.6%）、皮疹（40.9%，两组）、关节痛（39.1% vs 28.1%）、发热（38.7% vs 26.0%）、丙氨酸氨基转移酶升高（33.9% vs 22.8%）和脂肪酶升高（32.2% vs 27.4%）；阿替利珠单抗组 13%的患者和对照组 16%的患者因不良事件停止了所有治疗。
阿替利珠单抗联合维莫非尼和考比替尼的靶向治疗是安全且耐受良好的，并显著增加了 BRAF 突变阳性晚期黑色素瘤患者的无进展生存期。
F Hoffmann-La Roche 和 Genentech。
