Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
Eur J Cancer. 2023 Mar;181:145-154. doi: 10.1016/j.ejca.2022.12.012. Epub 2022 Dec 27.
The EPAZ study (NCT01861951) showed recently that pazopanib was non-inferior to doxorubicin in patients ≥60 years treated in first line for advanced soft tissue sarcoma . The current post-hoc analysis aimed to assess the prognostic impact of frailty.
Geriatric assessments were evaluated at baseline. Age >75 years, liposarcoma, ECOG = 2, G8 ≤14, instrumental activities of daily living (IADL) ≥1 and Charlson Comorbidity Index ≥2 were tested for their impact on progression-free survival (PFS), overall survival (OS), CTCAE grade 3/4 adverse events (AEs) or serious AEs (SAEs), using univariate and multivariate analysis models.
univariate analysis showed an increased risk of grade 3/4 AEs and SAEs for ECOG = 2, G8 score ≤14 or IADL ≥1, independent of treatment. The multivariate analysis exhibited for pazopanib a significantly reduced risk for grade 3/4 AEs (HR 0.53; p = 0.033), and in patients with G8 ≤14 an increased risk for SAEs (HR 2.67; p = 0.011). In the multivariate analysis, G8 ≤14 was a negative prognostic factor for PFS (HR 1.82; p = 0.009) and IADL ≥1 for OS (HR 2.02; p = 0.007). ECOG = 2 was the strongest negative predictor for PFS (HR 4.39; p = 0.001) and OS (HR 3.74; p = 0.004). Neither age nor Charlson Comorbidity Index showed any impact on PFS, OS, incidence of grade 3/4 AEs or SAEs.
This post hoc analysis demonstrated that age is not a denominator for outcome or toxicity in elderly patients with soft tissue sarcoma . Instead, geriatric and functional assessments should be used to counsel patients and tailor therapy to individual needs. Moreover, pazopanib has a reduced risk for grade 3/4 AEs compared to doxorubicin.
EPAZ 研究（NCT01861951）最近表明，帕唑帕尼在治疗 60 岁及以上晚期软组织肉瘤患者的一线治疗中不劣于多柔比星。本事后分析旨在评估虚弱的预后影响。
在基线时评估老年评估。年龄>75 岁、脂肪肉瘤、ECOG=2、G8≤14、工具性日常生活活动（IADL）≥1 和 Charlson 合并症指数≥2，用于无进展生存期（PFS）、总生存期（OS）、CTCAE 3/4 级不良事件（AE）或严重 AE（SAE）的单变量和多变量分析模型。
单变量分析显示，ECOG=2、G8 评分≤14 或 IADL≥1 与治疗无关，AE 或 SAE 发生 3/4 级的风险增加。多变量分析显示，帕唑帕尼治疗时，3/4 级 AE 的风险显著降低（HR0.53；p=0.033），G8≤14 的 SAE 风险增加（HR2.67；p=0.011）。多变量分析显示，G8≤14 是 PFS 的负预后因素（HR1.82；p=0.009），IADL≥1 是 OS 的负预后因素（HR2.02；p=0.007）。ECOG=2 是 PFS（HR4.39；p=0.001）和 OS（HR3.74；p=0.004）的最强负预测因子。年龄和 Charlson 合并症指数均未对 PFS、OS、3/4 级 AE 或 SAE 的发生率产生任何影响。
本事后分析表明，年龄不是老年软组织肉瘤患者结局或毒性的决定因素。相反，应使用老年和功能评估来为患者提供咨询并根据个体需求调整治疗。此外，与多柔比星相比，帕唑帕尼发生 3/4 级 AE 的风险降低。
