Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pulmonary Diseases, Pulmonic Oncology, Haga Hospital, The Hague, The Netherlands.
Drugs Aging. 2024 May;41(5):431-441. doi: 10.1007/s40266-024-01114-z. Epub 2024 May 10.
Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status.
This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors.
Patients aged 70 years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and "Tolerability and safety of immunotherapy study". Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3-5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment.
Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of < 15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of < 15 or a higher WHO score of 1 for having higher odds of toxicity [odds ratio (OR) 2.32 (95% CI 0.41-13.02); OR 1.33 (95% CI 0.45-4.17)], treatment discontinuation due to immune-related treatment toxicity [OR 2.25 (95% CI 0.61-8.31); OR 2.18 (95% CI 0.7-6.73)], and hospitalization due to immune-related treatment toxicity [OR 3.72 (95% CI 0.39-35.4); OR 1.31 (95% CI 0.35-4.9)]. Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1-2 toxicity as well.
Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1-2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity.
检查点抑制剂已成为治疗多种癌症的有效策略，包括老年患者。然而，患有癌症的老年患者是一个异质群体，他们在虚弱程度、认知能力和身体状况方面可能存在很大差异。
本研究旨在探讨临床虚弱与免疫相关治疗毒性、住院治疗以及因免疫相关治疗毒性而导致的治疗中断之间的关系，研究对象为接受检查点抑制剂治疗的老年癌症患者。
从 TENT 研究、IMAGINE 研究和“免疫疗法耐受性和安全性研究”中选择了 70 岁及以上接受检查点抑制剂治疗的患者。使用老年-8 测试评分和世界卫生组织（WHO）状态评估临床虚弱。结局为 3-5 级毒性、住院治疗和因毒性而导致的治疗中断。
在 99 名患者中，有 22%的患者存在合并症。尽管有 33%的患者因异常的老年-8 测试评分<15 而被认为虚弱，但 51%（WHO 评分 0）和 40%（WHO 评分 1）的患者不存在身体损伤。尽管该队列的样本量有限，但观察到具有异常老年-8 测试评分<15 或更高的 WHO 评分 1 的患者具有更高的毒性发生率[比值比（OR）2.32（95%置信区间 0.41-13.02）；OR 1.33（95%置信区间 0.45-4.17）]、因免疫相关治疗毒性而导致的治疗中断[OR 2.25（95%置信区间 0.61-8.31）；OR 2.18（95%置信区间 0.7-6.73）]和因免疫相关治疗毒性而导致的住院治疗[OR 3.72（95%置信区间 0.39-35.4）；OR 1.31（95%置信区间 0.35-4.9）]的可能性更高。此外，在亚分析中，我们还观察到，因免疫相关治疗毒性而导致的治疗中断也经常发生在毒性分级为 1-2 级的患者中。
尽管没有统计学意义，但在癌症老年患者的真实世界免疫治疗中，我们观察到，随着虚弱程度的增加，毒性、住院治疗和治疗中断的发生率呈一致趋势。需要更大规模的研究来证实这些探索性结果。此外，毒性分级为 1-2 级的老年患者经常早期停止治疗，这表明他们对毒性的耐受性较低。
