Background: Nivolumab and pembrolizumab, two PD1 inhibitors, trigger immune-related adverse events in approximately 50% of patients. Our objective was to determine whether these immune-related adverse events are associated with patient outcomes. Patients and Methods: Retrospective cohort study, realized at the Institut Universitaire du Cancer de Toulouse, of all the patients treated with nivolumab or pembrolizumab off clinical trials. We included patients (i) diagnosed with unresectable stage III or stage IV melanoma or with recurrent stage IIIB or stage IV non-small cell lung cancer (ii) on nivolumab 3mg/kg or pembrolizumab 2mg/kg every 2 or 3 weeks respectively. Results: Of the 311 patients included (of 641 eligible subjects), 120 (38.6%) had melanoma and 191 (61.4%) had non-small cell lung cancer; 241 (77.5%) were treated with nivolumab with a median follow-up of 24 months (20-29). We observed 166 immune-related adverse events in 116 (37.3%) patients, categorized as "early" (onset before 12 weeks in melanoma and before 8 weeks in lung cancer) in 63 (54.3%) patients. Early and late adverse events were significantly associated with an increase in overall survival: adjusted hazard ratio 0.58 [0.41-0.84] (p = .003) and 0.28 [0.16-0.50] (p < .001) respectively. The overall response rate was significantly increased in patients with an immune-related adverse event (53.9% vs 12.9%, p < .001) Conclusions: This study validates the association between immune-related adverse events and anti-PD1 efficacy in real-life, especially if these events are delayed. Our results, along with further studies on the place of immunosuppressive drugs in the therapeutic strategy, could improve the management of these adverse events.

中文翻译：

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在黑色素瘤和非小细胞肺癌中抗PD1治疗期间免疫相关不良事件的预后影响：一项现实生活的回顾性研究。

背景：Nivolumab和pembrolizumab这两种PD1抑制剂在大约50％的患者中引发免疫相关的不良事件。我们的目标是确定这些免疫相关的不良事件是否与患者预后相关。患者与方法：回顾性队列研究在图卢兹大学癌症研究所进行，对所有接受nivolumab或pembrolizumab治疗的患者进行了临床试验。我们纳入了（i）被诊断为不可切除的III期或IV期黑色素瘤或复发的IIIB期或IV期非小细胞肺癌的患者（ii）分别每2周或3周服用一次nivolumab 3mg / kg或pembrolizumab 2mg / kg的非小细胞肺癌。结果：纳入的311例患者（在641名合格受试者中）有120例（38.6％）患有黑色素瘤，而191例（61.4％）患有非小细胞肺癌。241（77。5％的患者接受了nivolumab的治疗，中位随访时间为24个月（20-29）。我们在116名（57.3％）患者中观察到116例（37.3％）患者中的166例与免疫相关的不良事件，分类为“早期”（黑色素瘤在12周之前发作，在肺癌8周之前发作）。早期和晚期不良事件与总体生存率显着相关：调整后的危险比分别为0.58 [0.41-0.84]（p = .003）和0.28 [0.16-0.50]（p <.001）。患有免疫相关不良事件的患者的总体缓解率显着提高（53.9％vs 12.9％，p <.001）结论：本研究验证了现实生活中免疫相关不良事件与抗PD1疗效之间的关联，尤其是如果这些事件被延迟。我们的结果