Clinical Outcomes of the Alternative GAMMA Regimen in Relapsed Germ Cell Tumours.

Abstract

Background: Following promising results in a phase II trial evaluating GAMMA as salvage therapy for relapsed germ cell tumours (GCT) who had progressed on cisplatin-based chemotherapy, the GAMMA regimen was adopted into clinical practice at St Bartholomew's Hospital. This study provides the largest real-world evaluation of the GAMMA regimen to date, assessing its long-term effectiveness in an unselected patient population. Methodology: This was a single-centre retrospective study of patients who progressed following cisplatin-based chemotherapy and were treated with GAMMA regimen between November 2012 and September 2023. Data collected included clinico-pathological features, treatment details and prognostic risk scores which are International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification and International Prognostic Factor Study Group (IPFSG) score. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were assessed. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Result(s): A total of 69 patients were included with a median age of 39 years. Most were male (94%) and had an ECOG performance status of 0-1 (76%). Non-seminomatous histology was observed in 80% and 74% had a gonadal primary tumour. BEP was the most common first-line treatment (89%). Poor-risk disease per IGCCCG criteria was seen in 41% while 39% were intermediate-risk by IPFSG. 64% completed all planned chemotherapy cycles; 10% discontinued due to toxicity. Stem cell mobilisation was successful in 91%. The most frequent treatment response was partial response marker negative (PRm-) (38%). The 2-year PFS and OS rates were 31% and 49%, respectively. By IPFSG risk group, 2-year PFS and OS ranged from 20%-50% and 20%-75%. Among patients with LDH >= 2.5xULN, 2-year PFS was 38% and OS was 47%. Conclusion(s): GAMMA demonstrates acceptable tolerability and maintains meaningful survival outcomes, supporting its use as a dose-intensified salvage treatment option for patients with relapsed GCT. Copyright © 2026 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.