Sakakida Tomoki, Ishikawa Takeshi, Uchino Junji, Tabuchi Yusuke, Komori Satoshi, Asai Jun, Arai Akihito, Tsunezuka Hiroaki, Kosuga Toshiyuki, Konishi Hirotaka, Hongo Fumiya, Inoue Masayoshi, Hirano Shigeru, Ukimura Osamu, Taguchi Tetsuya, Takayama Koichi, Itoh Yoshito
Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Oncol Lett. 2020 Oct;20(4):14. doi: 10.3892/ol.2020.11875. Epub 2020 Jul 15.
The number of elderly patients with cancer has increased due to aging of the population. However, safety of programmed cell death-1 (PD-1) or programed cell death ligand 1 (PD-L1) inhibitors in elderly patients remains controversial, and limited information exists in frail patients. The present study retrospectively identified 197 patients treated with nivolumab, pembrolizumab or atezolizumab for unresectable advanced cancer between September 2014 and December 2018. Patients were divided into the elderly (age, ≥75 years) and non-elderly (age, <75 years) groups. The detailed immune-related adverse events (irAE) profile and development of critical complications were evaluated. To assess tolerability, the proportion of patients who continued PD-1/PD-L1 inhibitor for >6 months was analyzed. In the two groups, a three-element frailty score, including performance status, Charlson Comorbidity Index and neutrophil-lymphocyte ratio, was estimated, and patients were divided into the low-, intermediate- and high-frailty subgroups. Safety and tolerability were evaluated using the aforementioned items. A total of 58 patients (29.4%) were aged ≥75 years. No significant difference was found in the development of irAEs, hospitalization and treatment discontinuation due to irAEs between the two groups. However, the occurrence of unexpected critical complications was significantly higher in the elderly group (P=0.03). Among the elderly patients with high frailty, more critical complications and fatal irAE (hepatitis) were observed. In this population, 33.3% were able to continue treatment for >6 months without disease progression. The present analysis based on real world data showed similar safety and tolerability of PD-1/PD-L1 inhibitors in elderly patients with advanced malignancies. However, the impact of irAE in elderly patients, especially those with frailty, was occasionally greater compared with that in younger and fit patients.
由于人口老龄化，老年癌症患者的数量有所增加。然而，程序性细胞死亡蛋白1（PD-1）或程序性细胞死亡配体1（PD-L1）抑制剂在老年患者中的安全性仍存在争议，而关于体弱患者的信息有限。本研究回顾性纳入了2014年9月至2018年12月期间接受纳武利尤单抗、帕博利珠单抗或阿特珠单抗治疗不可切除晚期癌症的197例患者。患者被分为老年组（年龄≥75岁）和非老年组（年龄<75岁）。评估了详细的免疫相关不良事件（irAE）谱和严重并发症的发生情况。为评估耐受性，分析了持续使用PD-1/PD-L1抑制剂超过6个月的患者比例。在两组中，评估了包括体能状态、Charlson合并症指数和中性粒细胞与淋巴细胞比值的三元衰弱评分，并将患者分为低、中、高衰弱亚组。使用上述指标评估安全性和耐受性。共有58例患者（29.4%）年龄≥75岁。两组之间在irAE的发生、因irAE住院和停药方面未发现显著差异。然而，老年组意外严重并发症的发生率显著更高（P=0.03）。在高衰弱的老年患者中，观察到更多严重并发症和致命性irAE（肝炎）。在该人群中，33.3%的患者能够在无疾病进展的情况下继续治疗超过6个月。基于真实世界数据的本分析显示，PD-1/PD-L1抑制剂在老年晚期恶性肿瘤患者中的安全性和耐受性相似。然而，与年轻健康患者相比，irAE对老年患者，尤其是体弱患者的影响偶尔更大。
