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Maintenance oral etoposide after high-dose chemotherapy (HDCT) for patients with relapsed metastatic germ-cell tumors (mGCT)

Published:January 17, 2023DOI:https://doi.org/10.1016/j.clgc.2023.01.004

      Clinical Practice points

      • This retrospective analysis evaluates the role of maintenance oral etoposide for up to 3 months in patients with relapsed NSGCT who completed HDCT and PBSCT.
      • Maintenance etoposide was offered to patients who achieved complete serologic remission and hematologic recovery after HDCT.
      • With the limitations of retrospective analysis, this study showed potential clinical benefit of maintenance oral etoposide therapy in patients with relapsed NSGCT who completed HDCT and PBSCT and achieved serologic remission and hematologic recovery.
      • On subgroup analysis, the benefit of oral etoposide seems more pronounced in patients with platinum-refractory disease.
      • Conversely, the addition of oral etoposide after HDCT did not significantly impact PFS and OS in patients with platinum-sensitive disease.
      • This treatment was associated with low treatment-related mortality
      • The cause of death in the etoposide cohort was disease progression in 62/65 patients, 3 patients died from secondary hematologic malignancies
      • It is difficult to delineate the value of maintenance of etoposide without evaluation in a prospective clinical trial.
      • A randomized phase II trial of maintenance etoposide vs observation in patients with relapsed NSGCT who completed HDCT as initial salvage with biomarkers evaluating minimal residual disease is currently enrolling at our institution (ClinicalTrials.gov Identifier: NCT04804007).

      Abstract:

      Background

      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 non-randomized retrospective analysis.

      Methods

      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.

      Results

      2-year PFS in the maintenance etoposide vs observation group was 55% vs 46% (p=0.028). 2-year OS was 61% vs 54% (p=0.04). 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<0.001).
      2-year OS and PFS for platinum-refractory patients who received maintenance etoposide vs observation group were 50.2% vs 26.1% (P<0.0001) and 44.2% vs 23.1% (P=0.0003) 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.

      Conclusions

      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).

      MicroAbstract

      This study reviews the outcomes of 383 patients with relapsed NSGCT who were treated at Indiana University between 2001 to 2019. Within the limitations of a retrospective analysis, this study demonstrates that daily oral etoposide therapy produced encouraging efficacy results in patients with relapsed NSGCT who completed HDCT and PBSCT and achieved complete serologic remission and hematologic recovery. These data have led to an ongoing randomized phase II clinical trial of maintenance etoposide vs observation post HDCT in relapsed germ-cell tumors (ClinicalTrials.gov Identifier: NCT04804007).
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