The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment-naïve and 22% failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67% of patients, grade 3-5 in 38%. The overall objective response rate was 41%, 57% in treatment-naïve and 21% in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0-6.0) in the whole cohort, 11.0 months (95% CI, 6.0-NR) in treatment-naïve and 2.0 months (95% CI, 1.4-4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.

中文翻译：

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在晚期黑色素瘤中联合ipilimumab和nivolumab一线治疗以及BRAF靶向治疗后。

ipilimumab和nivolumab的组合是一种用于转移性黑色素瘤的高活性全身疗法，但会引起明显的毒性。我们探索这种治疗方法在常规临床实践中的安全性和有效性，尤其是在以丝氨酸/苏氨酸蛋白激酶B-Raf（BRAF）为靶标的治疗方法中。回顾性分析了澳大利亚10所三级黑色素瘤机构中依立木单抗和nivolumab引发的不可切除的IIIC / IV期黑色素瘤的连续患者。收集的数据包括人口统计学，反应和生存结果。一共包括152例患者进行分析，其中39％为未接受过治疗的患者和22％失败的一线BRAF / MEK抑制剂。与治疗相关的不良事件发生在67％的患者中，3-5级发生在38％的患者中。总体客观回应率为41％，初治患者中有57％，BRAF / MEK衰竭患者中有21％。在整个队列中，无进展生存期的中位数为4.0个月（95％CI，3.0-6.0），未经治疗的中位无进展生存期为11.0个月（95％CI，6.0-NR），而在整个研究中为2.0个月（95％CI，1.4-4.6）。 BRAF / MEK衰竭患者。ipilimumab和nivolumab的组合可在现实世界的人群中安全有效地使用。虽然一线疗效似乎可与试验人群相媲美，但先前使用BRAF / MEK抑制剂治疗失败的BRAF突变患者的反应较少。