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Clinical Outcomes of the Alternative GAMMA Regimen in Relapsed Germ Cell Tumours
Nasreen Abdul Aziz1,2,3, Kenrick Ng2, Prabhakar Rajan2,4,5
1School of Medicine, School of Postgraduate Studies, Royal College of Surgeons in Ireland, Dublin, Ireland.
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.
Results:
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%.
Conclusions:
GAMMA demonstrates acceptable tolerability and maintains meaningful survival outcomes, supporting its use as a dose-intensified salvage treatment option for patients with relapsed GCT.
