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Mature results of the GETUG 13 phase III trial in poor-prognosis germ-cell tumors (GCT).
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2016
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Surgical OncologyCancer ManagementPathologyPoor-prognosis GctMetronomic ChemotherapyNeuro-oncologyOncologyGenitourinary CancerMetronomic TherapyPhase Iii TrialClinical TrialsRadiation OncologyMolecular OncologyCancer ResearchHealth SciencesCancer TreatmentMature ResultsGerm Cell NeoplasiaTumor MicroenvironmentTumor Marker DeclineImmune Checkpoint InhibitorMedicineGetug 13Stem Cell Transplant
4504 Background: Until 2014, standard treatment for poor-prognosis GCT was 4 BEP plus surgery and cure was achieved in only 50% of patients (pts) (IGCCCG 1997). The tumor marker decline rate identified pts with a better outcome (J Clin Oncol 2004, 22: 3868-76). The GETUG 13 phase III trial established that switching pts with an unfavorable decline to intensified chemotherapy results in improved progression-free survival (PFS) (Lancet Oncol 2014; 15: 1442-50). We assessed the long-term efficacy and toxicity in pts treated in GETUG 13. Methods: 263 pts with IGCCCG poor-prognosis GCT were treated with 1 BEP. hCG and AFP were assessed at day 21: 1) 51pts with a favorable decline continued BEP (Fav-BEP); 2) 203 pts with an unfavorable decline were randomized to receive either BEP (Unfav-BEP) or a dose-dense regimen (Unfav-dose-dense), consisting of paclitaxel-BEP plus oxaliplatin x 2 cycles, followed by 2 cycles of cisplatin, ifosfamide, and bleomycin + G-CSF. PFS and overall survival (OS) (logrank) and long-term toxicity (NCI-CTC criteria) were assessed. Results: The median follow-up is 5.6 years (range 0.3; 11.9). The 5-year PFS rate is 60% in the Unfav-dose-dense arm vs 47% in the Unfav-BEP arm (HR: 0.65 [0.43-0.97]; p=0.037). The 5-year OS rate is 70.4% and 60.8%, respectively (HR: 0.69 [0.43-1.11]; p=0.12). Side effects evolved favorably, with 3 pts in the Unfav-dose-dense arm reporting grade 3 motor neurotoxicity at 1 year but no reported toxicity ≥ grade 2 after year 2. The prognostic value of the tumor marker decline was confirmed: 70% vs 47% for 5-year PFS (p=0.006), and 78% vs 61% for OS (p=0.02). Salvage high-dose chemotherapy plus a stem cell transplant was implemented in 8% in the Unfav-dose-dense arm and 17% in the Unfav-BEP arm (p=0.035). Conclusions: With a mature follow-up, GETUG 13 shows that pts with poor-prognosis GCT and an unfavorable tumor marker decline after 1 BEP who are treated with intensified chemotherapy achieve significantly improved PFS, numerically better OS, minimal long-term toxicity, and a reduced need for high-dose salvage chemotherapy plus a stem cell transplant. These data support integrating this strategy as a standard of care for these rare pts. Clinical trial information: NCT00104676.