Taza Fadi, Abonour Rafat, Zaid Mohammad Abu, Althouse Sandra K, Anouti Bilal, Akel Reem, Hanna Nasser H, Adra Nabil, Einhorn Lawrence H
Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN.
Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN.
Clin Genitourin Cancer. 2023 Apr;21(2):213-220. doi: 10.1016/j.clgc.2023.01.004. Epub 2023 Jan 18.
HDCT and peripheral-blood stem-cell transplant (PBSCT) can cure up to 60% of pts with relapsed mGCT. Maintenance daily oral etoposide after salvage therapy has demonstrated potential clinical benefit. We now evaluate the potential role of maintenance etoposide versus observation post HDCT+PBSCT in this nonrandomized retrospective analysis.
The prospectively maintained Indiana University testicular cancer database was interrogated. Patients with relapsed non-seminoma who completed HDCT+PBSCT and achieved complete serologic remission and hematologic recovery were evaluated. Outcomes of pts who received maintenance etoposide (N = 141) were compared to pts who were observed (N = 242). In this retrospective study, Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Univariable and multivariable cox regression models were used to determine variables associated with PFS. We also performed an additional analysis to compare the survival outcomes in the platinum-refractory patients' subgroup based on maintenance etoposide treatment.
Two-year PFS in the maintenance etoposide vs observation group was 55% vs. 46% (P = .028). Two-year OS was 61% vs 54% (P = .04). A multivariable analysis was performed, including the factors: primary tumor site (testis vs. mediastinum), IGCCCG risk, platinum refractory, HDCT line of therapy (2nd vs ≥3rd), tumor marker amplitude at HDCT initiation, and receipt of maintenance etoposide post HDCT vs. observation. Maintenance etoposide was confirmed as an independent predictor of improved PFS with HR 0.51 [95% CI, 0.37-0.70] (P < .001). Two-year OS and PFS for platinum-refractory patients who received maintenance etoposide vs. observation group were 50.2% vs. 26.1% (P < .0001) and 44.2% vs.. 23.1% (P = .0003), respectively. There was no statistically significant difference in 2-year OS and PFS between the platinum-sensitive patients who received maintenance etoposide and those who were observed.
Daily oral etoposide therapy produced encouraging efficacy results in patients with relapsed non-seminoma GCT (NSGCT) who completed HDCT and PBSCT and achieved complete serologic remission and hematologic recovery. Patients with platinum-refractory disease and poor prognostic features are potential candidates for daily maintenance oral etoposide post HDCT. These data have led to an ongoing randomized phase II clinical trial (NCT04804007).
大剂量化疗（HDCT）和外周血干细胞移植（PBSCT）可治愈多达60%的复发性转移性生殖细胞肿瘤（mGCT）患者。挽救治疗后每日口服依托泊苷已显示出潜在的临床益处。我们现在在这项非随机回顾性分析中评估HDCT+PBSCT后维持依托泊苷与观察相比的潜在作用。
查询前瞻性维护的印第安纳大学睾丸癌数据库。对完成HDCT+PBSCT并实现完全血清学缓解和血液学恢复的复发性非精原细胞瘤患者进行评估。将接受维持依托泊苷治疗的患者（N = 141）与接受观察的患者（N = 242）的结局进行比较。在这项回顾性研究中，采用Kaplan-Meier方法分析无进展生存期（PFS）和总生存期（OS）。使用单变量和多变量cox回归模型确定与PFS相关的变量。我们还进行了一项额外分析，以比较基于维持依托泊苷治疗的铂耐药患者亚组的生存结局。
维持依托泊苷组与观察组的两年PFS分别为55%和46%（P = 0.028）。两年OS分别为61%和54%（P = 0.04）。进行了多变量分析，包括以下因素：原发肿瘤部位（睾丸与纵隔）、国际生殖细胞癌协作组（IGCCCG）风险、铂耐药、HDCT治疗线数（第2线与≥第3线）、HDCT开始时的肿瘤标志物幅度，以及HDCT后接受维持依托泊苷与观察。维持依托泊苷被确认为改善PFS的独立预测因素，风险比（HR）为0.51 [95%置信区间（CI），0.37 - 0.70]（P < 0.001）。接受维持依托泊苷治疗的铂耐药患者与观察组的两年OS和PFS分别为50.2%和26.1%（P < 0.0001）以及44.2%和23.1%（P = 0.0003）。接受维持依托泊苷治疗的铂敏感患者与接受观察的患者在两年OS和PFS方面无统计学显著差异。
对于完成HDCT和PBSCT并实现完全血清学缓解和血液学恢复的复发性非精原细胞瘤性生殖细胞肿瘤（NSGCT）患者，每日口服依托泊苷治疗产生了令人鼓舞的疗效结果。铂耐药疾病和预后不良特征的患者是HDCT后每日维持口服依托泊苷的潜在候选者。这些数据已促成一项正在进行的随机II期临床试验（NCT04804007）。
