Medical Oncology Clinic, Health Sciences University, Elazig City Hospital, Elazig, Turkey.
Hematology-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
J Geriatr Oncol. 2024 May;15(4):101742. doi: 10.1016/j.jgo.2024.101742. Epub 2024 Mar 11.
Immune checkpoint inhibitors (ICIs) became a treatment option in most tumor types and improved survival in patients with cancer in the last decade. Older patients with cancer are underrepresented in the pivotal clinical trials with ICIs. Older patients with cancer often have significant comorbidities and geriatric syndromes like frailty, which can complicate cancer care and treatment decisions. Frailty is among the most prevalent geriatric syndromes in patients with cancer and could lead to inferior survival and a higher risk of complications in patients treated with chemotherapy. However, the effect of frailty on the efficacy and safety of ICIs is understudied. This review focuses on the available evidence regarding the association between frailty and ICI efficacy and safety. Although the survival benefits of ICIs have generally been shown to be independent of age, the available real-world data has generally suggested higher rates of immune-related adverse events (irAEs) and treatment discontinuation in older patients. While international organizations recommend conducting a comprehensive geriatric assessment CGA to assess and address frailty before the start of anti-cancer therapies, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher is frequently used in clinical practice as synonymous with frailty, albeit with significant limitations. The available data has generally demonstrated diminished ICI efficacy in patients with an ECOG 2 or higher compared to patients with better performance status, while the incidence of high-grade irAEs were similar. Whilst evidence regarding outcomes with ICI in older patients and in those with sub-optimal performance status is growing, there is very limited data specifically evaluating the role of frailty with ICIs. These studies found a shortened overall survival, yet no evidence of a lower response rate to ICIs. These patients experienced more AEs, but they did not necessarily have a higher incidence of irAEs.
免疫检查点抑制剂 (ICIs) 在过去十年中成为大多数肿瘤类型的治疗选择，并改善了癌症患者的生存率。在具有ICI 的关键临床试验中，癌症老年患者代表性不足。患有癌症的老年患者常有重大合并症和老年综合征，如虚弱，这可能会使癌症护理和治疗决策复杂化。虚弱是癌症患者中最常见的老年综合征之一，可能导致接受化疗的患者生存质量下降和并发症风险增加。然而，虚弱对 ICI 疗效和安全性的影响尚未得到充分研究。本综述重点介绍了关于虚弱与 ICI 疗效和安全性之间关联的现有证据。尽管 ICI 的生存获益通常与年龄无关，但现有真实世界数据普遍表明，老年患者的免疫相关不良事件 (irAE) 和治疗中断率更高。虽然国际组织建议在开始抗肿瘤治疗之前进行全面的老年评估 (CGA) 来评估和解决虚弱问题，但在临床实践中，ECOG 体能状态 2 或更高通常被用作虚弱的代名词，尽管存在重大局限性。现有数据普遍表明，与体能状态更好的患者相比，ECOG 2 或更高的患者的 ICI 疗效降低，而高级别 irAE 的发生率相似。虽然关于老年患者和体能状态不佳的患者使用 ICI 的结果的证据不断增加，但专门评估 ICI 与虚弱关系的数据非常有限。这些研究发现总生存期缩短，但没有证据表明对 ICI 的反应率降低。这些患者经历了更多的 AE，但他们不一定有更高的 irAE 发生率。
