Department of Medicine, McGill University, Montreal, Canada.
Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Canada.
Sci Rep. 2020 Sep 3;10(1):14607. doi: 10.1038/s41598-020-71788-z.
The 'real-world' patient population of metastatic melanoma is not fully represented in clinical trials investigating checkpoint inhibitors. We described therapy discontinuation in an unselected population-based cohort of adults with metastatic melanoma who started therapy with pembrolizumab, nivolumab, or nivolumab/ipilimumab from January 2015 to August 2017. Therapy discontinuation was defined as a gap between doses beyond 120 days, and/or initiation of another cancer therapy. We estimated drug-specific rate ratios for therapy discontinuation adjusted for age, sex, comorbidities, health care use, and past cancer therapies. We included 876 metastatic melanoma patients initiating pembrolizumab (44.3%), nivolumab/ipilimumab (31.2%), and nivolumab (24.5%). At 12 months of follow-up, the probabilities of therapy discontinuation were 49.9% (95% confidence interval, CI 43.6-56.5) for pembrolizumab, 58.8% (95% CI 50.5-67.3) for nivolumab, and 59.2% (95% CI 51.7-66.8) for nivolumab/ipilimumab. Stratified analyses based on prior cancer therapy, brain metastases at baseline, and sex showed similar trends. In multivariable analyses, compared with pembrolizumab, patients starting nivolumab (rate ratio 1.38, 95% CI 1.08-1.77) or nivolumab/ipilimumab (rate ratio 1.30, 95% CI 1.02-1.65) were more likely to discontinue therapy. Our findings indicate frequent discontinuations of checkpoint inhibitors at one year. The lower discontinuation associated with pembrolizumab should be confirmed in further studies.
在研究检查点抑制剂的临床试验中，转移性黑色素瘤的“真实世界”患者人群并未得到充分体现。我们描述了从 2015 年 1 月至 2017 年 8 月，在接受派姆单抗、纳武单抗或纳武单抗/伊匹单抗治疗的未选择的基于人群的转移性黑色素瘤成年患者中，停药情况。停药定义为剂量间隔超过 120 天，和/或开始另一种癌症治疗。我们根据年龄、性别、合并症、医疗保健使用情况和既往癌症治疗情况，调整了特定药物的停药率比。我们纳入了 876 名开始接受派姆单抗（44.3%）、纳武单抗/伊匹单抗（31.2%）和纳武单抗（24.5%）治疗的转移性黑色素瘤患者。在 12 个月的随访期间，派姆单抗、纳武单抗和纳武单抗/伊匹单抗停药的概率分别为 49.9%（95%置信区间，43.6-56.5）、58.8%（95%置信区间，50.5-67.3）和 59.2%（95%置信区间，51.7-66.8）。基于既往癌症治疗、基线时脑转移和性别进行的分层分析显示出相似的趋势。多变量分析显示，与派姆单抗相比，开始接受纳武单抗（率比 1.38，95%置信区间 1.08-1.77）或纳武单抗/伊匹单抗（率比 1.30，95%置信区间 1.02-1.65）治疗的患者更有可能停止治疗。我们的研究结果表明，在一年内经常停止使用检查点抑制剂。在进一步的研究中，应确认派姆单抗相关的停药率较低。
