Multicenter analysis of high-dose chemotherapy (HDCT) regimens for recurrent germ cell tumors (GCTs).
Authors: Zugman Miguel , Shodiya Michael Olufemi , Maldonado Edward , Othman Tamer , Ebrahimi Hedyeh , Barragan-Carrillo Regina , Li Xiaochen , Rock Adam , Tripathi Abhishek , Pal Sumanta Kumar , Dorff Tanya B. , Zhumkhawala Ali , Hoeg Rasmus Tetens , Oliai Caspian , Mei Matthew Genyeh , Chehrazi-Raffle Alex 
Published: February 2025

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Background:
HDCT is an established salvage treatment for patients (pts) with recurrent germ cell tumors (GCTs). However, comparative analyses between contemporary HDCT approaches are lacking. This study presents an updated, multi-center analysis of the two most commonly used HDCT regimens: 1) Carboplatin 700 mg/m² and etoposide 750 mg/m² (CE) for two cycles, and 2) Carboplatin AUC 7-8 and etoposide 400 mg/m² for three cycles following two cycles of paclitaxel 200 mg/m² and ifosfamide 2000 mg/m² (TICE). We also included less common high-dose carboplatin-based regimens.
Methods:
Data from four high-volume referral centers were pooled and included pts treated with HDCT for recurrent GCTs between 1/1/2010 and 1/1/2024. Pts received either CE, TICE, or other regimens, though formal comparisons focused on the CE and TICE cohorts. Statistical tests used included Fisher’s exact test and Wilcoxon rank-sum test for qualitative and quantitative variables, respectively. Kaplan-Meier and log-rank tests were used to estimate and compare relapse-free survival (RFS) and overall survival (OS). Analyses were conducted using R Statistical Software, version 4.3.1.
Results:
A total of 111 pts were included: 50 received CE (45%), 32 received TICE (29%), and 29 received other high-dose carboplatin-based regimens (26%). Median age at diagnosis was 28.5 years (range 14-58), with the majority being Hispanic (56.8%) and having non-seminomatous GCT (76.6%). Six (12%) and four (12.5%) pts in the CE and TICE cohorts, respectively, had primary mediastinal disease. Late relapses, defined as disease recurrence occurring more than 2 years after first-line treatment, were rare, affecting 1 pt (3%) from the CE cohort and 3 pts (6%) in the TICE cohort. Most pts (43.2%) had International Germ Cell Cancer Collaborative Group poor risk disease at diagnosis. HDCT was administered as second-line therapy in 47.7% of patients and as third-line or beyond in 51.4%, with comparable distribution between TICE (53.1%) and CE (46%). patients receiving transplant as third-line (p=0.459). After a median follow-up of 55.5 months post-transplant, no significant difference in median RFS was observed between TICE and CE (10.2 vs 5.9 months; HR 0.91, 95% CI [0.54, 1.51], p = 0.706). There was a trend toward improved median OS for TICE compared to CE (57.2 vs 19.8 months; HR 0.67, 95% CI [0.37, 1.2], p = 0.18). Previously published prognostic scores using the Beyer, Einhorn, and International Prognostic Factor Study Group models accurately stratified pts by RFS and OS. Subgroup analysis suggested a possible benefit of TICE over CE in higher-risk patients.
Conclusions:
This multicenter analysis found no significant difference in RFS between the CE and TICE regimens though a trend toward improved OS with TICE was observed, particularly in pts with higher-risk disease.