Prescrire Int. 2016 Dec;25(177):289-292.
Existing drugs are poorly effective in patients with inoperable or meta- static melanoma without a mutation in the BRAF gene at position V600. The first-line treatment of choice for patients with BRAF V600-positive melanoma is a combination of dabrafenib (a BRAF inhibitor) and trametinib. Nivolumab is a human monoclonal antibody designed to block receptors for PD-1 (programmed cell death-1) and thus to enhance T lymphocyte activity, especially against tumour cells. Nivolumab has been authorised in Europe as monotherapy for patients with inoperable or metastatic melanoma, regardless of BRAFV600 status. Nivolumab has not been compared with the dabrafenib + trametinib combination in patients with BRAF V600-positive melanoma. A randomised double-blind trial ver- sus dacarbazine involved 418 patients with inoperable or metastatic BRAF V600-negative melanoma who had not yet received medication for this stage of the disease.The trial was halted prematurely when an unscheduled analysis showed an improvement in one-year survival with nivolumab compared to dacarbazne(73% versus 42%, p<0.0001). A double-blind trial compared first-line treatment with nivolumab, ipili- mumab or a combination of the two drugs.The mortality results are not yet available in mid-2016.The median time to melanoma aggravation or death was 6.9 months in the nivolumab group, 2.9 months in the ipilmumab group, and 11.5 months with the com- bination (p<0.001). A comparative, randomised, unblinded trial included 405 patients with metastatic or inoperable melanoma in whom at least one drug had failed. An interim analysis conducted after about two years showed no stat- istically significant difference in medi- an survival between patients who received nivolumab and those who received cytotoxic drugs. As expected, given its protein structure and mechanism, the adverse effects of nivolumab are mainly due to immunological mechanisms.They are numerous and affect many organs: skin rash and toxic epidermal necrolysis, thyroid dysfunction, hepatitis, pneumonia, colitis and encephalitis. Adverse effects were serious in 9% of patients, and a few cases were fatal. In practice, first-line nivolumab monotherapy was significantly more effective than dacarbazine in a trial in patients with BRAF V600-negative inoperable or metastatic melanoma. Although its evaluation must continue, nivolumab already seems to be a better option than dacarbazine and ipilimumab for treatment-naive patients, provided they receive detailed and balanced information on the uncertainties, efficacy and adverse effects of this new drug. For other patients, there is no evidence that nivolumab monotherapy represents an advantage over other available treatments.
对于无法手术或发生转移且BRAF基因V600位点无突变的黑色素瘤患者，现有药物疗效不佳。BRAF V600阳性黑色素瘤患者的一线治疗选择是达拉非尼（一种BRAF抑制剂）与曲美替尼联合使用。纳武单抗是一种人源单克隆抗体，旨在阻断程序性死亡受体1（PD - 1），从而增强T淋巴细胞活性，尤其是针对肿瘤细胞的活性。在欧洲，纳武单抗已被批准作为无法手术或转移性黑色素瘤患者的单一疗法，无论其BRAF V600状态如何。在BRAF V600阳性黑色素瘤患者中，尚未将纳武单抗与达拉非尼 + 曲美替尼联合用药进行比较。一项与达卡巴嗪对比的随机双盲试验纳入了418例无法手术或转移性BRAF V600阴性黑色素瘤患者，这些患者尚未接受针对该疾病此阶段的治疗。当一项非计划分析显示纳武单抗组的一年生存率高于达卡巴嗪组（73%对42%，p<0.0001）时，该试验提前终止。一项双盲试验比较了纳武单抗、伊匹单抗或两种药物联合作为一线治疗的效果。截至2016年年中，死亡率结果尚未得出。纳武单抗组黑色素瘤恶化或死亡的中位时间为6.9个月，伊匹单抗组为2.9个月，联合用药组为11.5个月（p<0.001）。一项比较性、随机、非盲试验纳入了405例转移性或无法手术的黑色素瘤患者，这些患者至少有一种药物治疗失败。在大约两年后进行的中期分析显示，接受纳武单抗治疗的患者与接受细胞毒性药物治疗的患者的中位生存期无统计学显著差异。正如预期的那样，鉴于其蛋白质结构和作用机制，纳武单抗的不良反应主要归因于免疫机制。不良反应众多，累及多个器官：皮疹和中毒性表皮坏死松解症、甲状腺功能障碍、肝炎、肺炎、结肠炎和脑炎。9%的患者出现严重不良反应，少数病例致命。实际上，在一项针对BRAF V600阴性无法手术或转移性黑色素瘤患者的试验中——纳武单抗一线单一疗法比达卡巴嗪显著更有效。尽管对其评估仍需继续，但对于未接受过治疗的患者而言，纳武单抗似乎已经是比达卡巴嗪和伊匹单抗更好的选择，前提是他们能获得关于这种新药的不确定性、疗效和不良反应的详细且平衡的信息。对于其他患者，没有证据表明纳武单抗单一疗法比其他现有治疗方法更具优势。
