University of Colorado, Aurora, CO, USA.
Princess Margaret Cancer Centre, Toronto, ON, Canada.
Cancer Treat Rev. 2020 Apr;85:101979. doi: 10.1016/j.ctrv.2020.101979. Epub 2020 Feb 4.
The combination of an anti-programmed death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) monoclonal antibody with platinum-based chemotherapy can improve outcomes for patients with advanced non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) compared with chemotherapy alone. For patients receiving these new treatment regimens, it is important that toxicities be managed effectively. A particular challenge can be determining the etiology of an event, especially when there are overlapping symptoms that can be attributed to either immunotherapy or to platinum-based chemotherapy. Here, we evaluate adverse events (AEs) reported in clinical trials of combination therapy with an anti-PD-1 or anti-PD-L1 (anti-PD-[L]1) immunotherapy and chemotherapy to provide information on toxicity management.
We performed a systematic review of the literature focused on randomized controlled trials of anti-PD-(L)1 therapy combined with platinum-based chemotherapy for advanced/metastatic NSCLC and SCLC.
Eleven reports from 9 randomized studies evaluating pembrolizumab, nivolumab, and atezolizumab combined with platinum-based chemotherapy in patients with advanced lung cancer were identified. Immune-mediated AEs and infusion reactions occurred more commonly in patients who received anti-PD-(L)1 immunotherapy with platinum-based chemotherapy compared with chemotherapy alone; however, there was no evidence of unexpected or unanticipated toxicity with these combinations.
Combinations of anti-PD-(L)1 immunotherapy with platinum-based chemotherapy regimens improve outcomes for patients with NSCLC and SCLC, and toxicity is generally manageable. Strategies for appropriate workup of AEs to allow clinicians to make informed decisions regarding causality and treatment modifications when appropriate are an important element of management of patients receiving an anti-PD-(L)1 agent combined with platinum-based chemotherapy.
与单独化疗相比，抗程序性死亡 1（PD-1）或抗程序性死亡配体 1（PD-L1）单克隆抗体与铂类化疗药物联合使用可改善晚期非小细胞肺癌（NSCLC）或小细胞肺癌（SCLC）患者的预后。对于接受这些新治疗方案的患者，有效管理毒性非常重要。确定事件的病因尤其具有挑战性，尤其是当存在可归因于免疫疗法或铂类化疗的重叠症状时。在这里，我们评估了抗 PD-1 或抗 PD-L1（抗 PD-[L]1）免疫疗法与化疗联合治疗的临床试验中报告的不良事件（AE），以提供有关毒性管理的信息。
我们对专注于抗 PD-（L）1 疗法联合铂类化疗治疗晚期/转移性 NSCLC 和 SCLC 的随机对照试验进行了系统评价。
在评估 pembrolizumab、nivolumab 和 atezolizumab 联合铂类化疗治疗晚期肺癌的 9 项随机研究中，共确定了 11 项报告。与单独化疗相比，接受抗 PD-（L）1 免疫治疗联合铂类化疗的患者更常发生免疫介导的 AE 和输液反应；然而，这些组合没有出现意外或意料之外的毒性。
抗 PD-（L）1 免疫疗法联合铂类化疗方案改善了 NSCLC 和 SCLC 患者的预后，且毒性通常可管理。对于接受抗 PD-（L）1 药物联合铂类化疗的患者，正确处理 AE 以允许临床医生在适当的情况下就因果关系和治疗修改做出明智决策的策略是管理的重要组成部分。
