Multicenter analysis of high-dose chemotherapy (HDCT) regimens for the treatment of patients (pts) with recurrent germ cell tumors (GCTs).
Authors: Chehrazi-Raffle Alex , Shodiya Michael Olufemi , Maldonado Edward , Othman Tamer , Ebrahimi Hedyeh , Barragán Carrillo Regina , Li Xiaochen , Rock Adam , Tripathi Abhishek , Pal Sumanta Kumar , Dorff Tanya B. , Zhumkhawala Ali , Hoeg Rasmus , Oliai Caspian , Olin Rebecca L. , Mei Matthew Genyeh 
Published: June 2024

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Background: Although HDCT is an established salvage treatment for pts with GCTs, there is no multi-center comparative analysis of the two most common dosing regimens: 1.) carboplatin 700 mg/m2 and etoposide 750 mg/m2 (CE) given for two cycles, and 2.) carboplatin AUC 7-8 and etoposide 400 mg/m2 given for three cycles, typically after two cycles of paclitaxel 200 mg/m2 and 2000 mg/m2x (TICE). To address this gap, we pooled data from four high-volume referral centers to evaluate the clinical efficacy of HDCT approaches. Methods: Demographic and clinical characteristics were retrospectively abstracted from electronic medical charts. Adult pts who received HDCT for recurrent GCT from 1/1/2010 to 1/1/2023 and received either CE or TICE were included. Differences among groups were tested using the Fisher's exact and the Wilcoxon rank-sum tests for qualitative and quantitative variables, respectively. Relapse-free survival (RFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method and log-rank test. All statistical analyses were conducted in R Statistical Software, version 4.3.1. Results: Seventy-two pts were identified across four institutions, of whom 46 received CE (64%) and 26 received TICE (36%). Most CE pts were treated at UCSF (39%) or UCLA (22%); TICE was predominantly given at COH (46%) or UCSF (46%). Median age at diagnosis was 30 (range, 18-58), a majority were Hispanic (51%), and most pts had a non-seminomatous GCT (79%). Ethnicity and tumor histology were similar between all two cohorts (P=NS for both). Most pts had Stage IIIC disease at diagnosis (44%) and most received HDCT in the 3rd line setting (71%). Tumor marker normalization prior to HDCT was more prevalent among CE (35%) than TICE (15%). Most pts who received CE (89%) and TICE (77%) completed their planned two and three cycles of HDCT, respectively. With a median follow-up of 54.0 months from the date of the last transplant, no difference was observed in the median RFS between TICE vs CE (10.2 vs 4.5 months, HR of 0.87, 95% CI [0.51, 1.49], P=0.610. We observed a trend toward improved median OS between TICE vs CE (56.5 vs 17.9 months, HR 0.54, 95% CI [0.29, 1.01], P=0.057). There was no difference between the rates of post-transplant relapse among pts who received HDCT in the 2nd line vs 3rd line (76.9% vs 61.7%, P=0.51). Conclusions: In the first multicenter comparative analysis of contemporary HDCT regimens, there was no difference in RFS between CE and TICE. However, we observed a trend toward improved survival among pts who received TICE. Additionally, we detected no difference in the rates of post-transplant relapse among pts treated in the 2nd line versus the 3rd line, supporting the application of HDCT in either setting. These findings represent the first of an ongoing regional collaboration that aims to leverage real-world data to improve clinical outcomes for pts with recurrent GCTs.