Background: Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study aimed to evaluate whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer (NSCLC).
Patients and methods: We conducted a retrospective study of patients who received nivolumab monotherapy at Sendai Kousei Hospital (n = 70). The patients were categorized into two groups based on the incidence of irAEs: those with irAEs (irAE group) or those without (non-irAE group). Treatment efficacy was evaluated in each group. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were determined.
Results: The objective response rate was 57% in the irAE group versus 12% in the non-irAE group. Median progression-free survival was 12.0 months in the irAE versus 3.6 months in the non-irAE group. The incidence of both irAEs and pre-existing antithyroid antibody was significantly higher in responders than in nonresponders. Multivariate analysis identified incidence of irAEs and pre-existing antithyroid antibody as an independent predictor of treatment response.
Conclusion: Objective response rate and progression-free survival were significantly better in the irAE than in the non-irAE group in patients with advanced NSCLC treated with nivolumab monotherapy. The development of irAEs was associated with clinical efficacy, and the presence of pre-existing antithyroid antibody might be correlated with treatment response to nivolumab monotherapy.
Implications for practice: Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study evaluted whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer. Results showed that the objective response rate and progression-free survival were significantly better in the patients who developed irAEs than in the patients who did not develop irAEs, and the incidence of irAEs and positivity for antithyroid antibody at pretreatment were independent predictors of treatment response of nivolumab monotherapy. Therefore, the development of irAEs predicts clinical benefit and suggests that cautious management of irAEs can lead to achieving maximum clinical benefit from nivolumab monotherapy.
摘要
背景。 免疫相关不良事件 (irAE) 经常发生在纳武单抗单药治疗中。本研究旨在评估 irAE 发生是否与晚期非小细胞肺癌 (NSCLC) 的治疗反应相关。
患者和方法。 我们对在 Sendai Kousei 医院 (n=70) 接受纳武单抗治疗的患者进行了一项回顾性研究。根据 irAE 发生率将患者分为两组:出现 irAE 患者组( irAE 组)或未出现 irAE 患者组(非‐irAE 组)。评估各组的治疗效果。将患者进一步分为应答者和无应答者,并确定治疗反应的预测因素。
结果。 irAE 组和非‐irAE 组的客观有效率分别为57%和12%。irAE 组和非‐irAE 组的中位无进展生存期分别为12.0个月和3.6个月。应答者的 irAE 和既往抗甲状腺抗体的发生率均显著高于无应答者。多因素分析发现,irAE 和既往抗甲状腺抗体的发生率是治疗反应的独立预测指标。
结论。 在接受纳武单抗单药治疗的晚期 NSCLC 患者中,irAE 组客观有效率和无进展生存期明显优于非‐irAE 组。irAE 的发生与临床疗效有关,而既往抗甲状腺抗体的存在可能与纳武单抗单药的治疗反应有关。
实践意义: 纳武单抗单药治疗频繁出现免疫相关不良事件 (irAE)。本研究评估了 irAE 进展与晚期非小细胞肺癌治疗反应是否相关。结果表明,客观有效率和无进展生存期在发生 irAE 的患者中明显好于未发生 irAE 的患者,治疗前 irAE 的发生率和抗甲状腺抗体的阳性率是纳武单抗单药治疗效果的独立预测指标。因此,通过 irAE 发生可以预测临床受益,并且表明,谨慎管理 irAE 可以使纳武单抗单药治疗获得最大临床受益。
Keywords: Antithyroid antibody; Immune checkpoint inhibitor; Immune‐related adverse event; Nivolumab; Non‐small‐cell lung cancer.
© AlphaMed Press 2018.