Standard-dose salvage chemotherapy in patients with refractory metastatic germ-cell tumors (mGCT) progressing after high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplant (PBSCT).

Abstract

e17061 Background: About 40% of patients with relapsed GCT will progress after HDCT and PBSCT and are generally incurable with further standard dose chemotherapy. We previously evaluated standard dose cisplatin combination chemotherapy in 15 patients following progression from HDCT and observed only a single brief PR ( JCO 18(6), 1181-1186.). We report results of non-platinum standard-dose chemotherapy regimens in refractory mGCT. Methods: Pts with mGCT who progressed after HDCT+PBSCT at Indiana University from 2004-2019 were evaluated. Kaplan-Meier methods and log-rank tests were used to analyze PFS and OS for the regimen directly following HDCT. Results: 78 pts with refractory mGCT were reviewed. 64 pts. (82%) received paclitaxel+gemcitabine (TG), 10 pts. (13%) received daily oral etoposide (E), and 4 pts. (5%) received oxaliplatin-based (O) regimens (oxaliplatin+gemcitabine or oxaliplatin+bevacizumab). Median age was 29 (range, 16-57). Primary site was testis in 62, retroperitoneum in 6, mediastinum in 9. Metastatic sites included retroperitoneal LNs (62), pulmonary (58), liver (23), bone (6), and brain (21). IGCCCG risk was good in 16, intermediate in 5, and poor in 57. HDCT was utilized as 2nd line setting in 72 pts, and ≥3rd line in 6 pts. Median time from HDCT to progression was 4 months (upper limit 16.6 months). PS and OS data is shown in the table, with superior outcomes in TG compared to O and E (p < 0.001). Maintenance oral etoposide after HDCT was administered in 44% (n = 28) of all patients who later progressed and received TG. Among 12 patients (19%) with 12-month PFS on TG, the median overall PFS was 18.3 months with 2 patients alive at the time of last follow-up. The primary site was testis in 11 patients, 67% (n = 8) were platinum refractory, and 83% (n = 10) were IGCCCG poor risk. 10 patients achieved a PR to TG, and two patients achieved CR. Conclusions: Salvage standard-dose chemotherapy with paclitaxel+gemcitabine after progression on HDCT is superior to oral etoposide or oxaliplatin-based regimens and should be the preferred regimen in patients with refractory mGCT. [Table: see text]