Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, the Netherlands.
Department of Gerontology and Geriatrics, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, the Netherlands.
Eur J Cancer. 2024 Nov;212:115056. doi: 10.1016/j.ejca.2024.115056. Epub 2024 Sep 30.
Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.
Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.
The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44).
Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.
辅助抗 PD-1 治疗可改善 III 期黑色素瘤的无复发生存期，但也会导致免疫相关不良事件（irAEs）。由于合并症和虚弱，老年患者尤其受到关注，这可能会影响他们对 irAEs 的耐受能力和从抗 PD-1 治疗中获益的能力。本研究旨在探讨临床参数与接受辅助抗 PD-1 治疗的根治性切除 III 期/IV 期皮肤黑色素瘤老年患者发生≥3 级 irAEs 和无复发生存期（RFS）之间的关系。
本研究使用全国性荷兰黑色素瘤治疗登记处（DMTR）的真实世界数据，选择了 2018 年至 2022 年期间接受辅助抗 PD-1 治疗的年龄≥65 岁、接受根治性切除 III 期/IV 期皮肤黑色素瘤治疗的患者。使用单变量和多变量逻辑回归比较了发生≥3 级 irAEs 的决定因素，并拟合单变量和多变量 Cox 比例风险模型以确定影响 RFS 的因素。
本研究共纳入 885 例患者，其中 280 例年龄≥75 岁。65-74 岁年龄组和≥75 岁年龄组≥3 级 irAEs 的发生率分别为 15.5%和 13.9%。年龄与≥3 级 irAEs 之间无显著相关性。然而，合并症数量的增加与发生≥3 级 irAEs 的风险增加相关（多变量分析：OR 1.83，95%CI 0.99-3.40）。本研究的 1 年 RFS 率为 80.0%，与之前的登记试验和真实世界数据报告的结果相当。存在≥3 种合并症与 RFS 下降显著相关（HR：1.68，95%CI 1.15-2.44）。
与之前试验中的老年亚组相比，老年患者接受辅助免疫治疗的获益相似。然而，合并症较多的患者发生≥3 级 irAEs 的风险增加，RFS 降低。在决定辅助治疗时应考虑到这一点。
