PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译：

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在晚期肺癌中联合化疗和程序性死亡1 /程序性死亡配体1抑制剂治疗的毒性管理。

目的将抗编程死亡1（PD-1）或抗编程死亡配体1（PD-L1）单克隆抗体与铂类化学疗法联合使用可改善晚期非小细胞肺癌（NSCLC）患者的预后）或小细胞肺癌（SCLC）与单纯化疗相比。对于接受这些新治疗方案的患者，重要的是要有效地控制毒性。一个特殊的挑战可能是确定事件的病因，尤其是当存在可归因于免疫疗法或基于铂类化学疗法的重叠症状时。在这里，我们评估在抗PD-1或抗PD-L1（anti-PD- [L] 1）免疫疗法和化学疗法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。方法我们对抗PD-（L）1治疗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文献综述。结果从9项随机研究中评估出11份报告，评估了pembrolizumab，nivolumab和atezolizumab联合铂类化疗治疗晚期肺癌。与单纯化疗相比，接受铂类化学疗法抗PD-（L）1免疫疗法的患者中，免疫介导的AE和输注反应更常见。但是，没有证据表明这些组合会产生意想不到的或无法预料的毒性。结论抗PD-（L）1免疫疗法与铂类化疗方案的组合可改善NSCLC和SCLC患者的预后，而且毒性通常是可以控制的。适当检查不良事件的策略，以使临床医生在适当的时候就因果关系和治疗方案做出明智的决定，这是接受抗PD-（L）1药物与铂类化学疗法联合治疗的患者管理的重要内容。