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.
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.
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.
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).
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).