Up to 50% of men with poor prognosis non-seminoma GCT die with standard BEP chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), met response targets in a phase II, multicentre, open-label, randomized trial (74% with complete response or partial response marker negative, 90% CI 61% to 85%; primary outcome). Here, we report long term outcomes and prognostic factors.
Patients with extracranial GCT and IGCCCG poor prognosis features were randomised to 4xBEP or CBOP/BEP (2xCBOP, 2xBO, 3xBEP with bleomycin dose 15,000iu). Low-dose, stabilising chemotherapy prior to entry was permitted. This analysis focuses on progression-free survival (PFS), overall survival (OS) and toxicity (all secondary outcomes), and exploratory analysis of prognostic factors and the impact of marker decline (as defined in GETUG13).
89 patients (43 CBOP/BEP) were randomised. After median 63 months follow-up, 3-year PFS is 55.7% (95% CI 39.7%, 69.0%) for CBOP/BEP arm, 38.7% (24.7%, 52.4%) for BEP (HR 0.59 (0.33, 1.06), p = 0.079). 3-year OS is 65.0% (48.8%, 77.2%) and 58.5% (43.0%, 71.2%) respectively (HR 0.79 (0.41, 1.52), p = 0.49). 12-month toxicity was affected by subsequent treatments, with no clear differences between arms. There was no grade ≥3 toxicity in the CBOP/BEP arm. In multivariate models, use of pre-protocol chemotherapy was the only factor associated with poorer PFS (HR2.09 (1.14, 3.81), p = 0.017). Mediastinal primary (HR 2.13 (1.02, 4.46), p = 0.045) and use of pre-protocol chemotherapy (HR 3.40 (1.74, 6.63), p < 0.001) were associated with poorer OS. Unfavourable marker decline, in 60 (70%) patients, was not associated with other prognostic factors, nor with long term outcomes (HR 0.82 (0.44, 1.53), p = 0.54 for PFS).
The trial was not powered to compare PFS and OS, but PFS results for CBOP/BEP are promising, and similar to the intensive arm of GETUG13. Impact on OS was less clear (and will be affected by subsequent therapy). Use of pre-protocol chemotherapy was associated with poorer outcomes. Further study in an international phase III trial is warranted.
Clinical trial identification
Legal entity responsible for the study
Medical Research Council, UK.
Cancer Research UK (grant no CRUK/05/014).
R.A. Huddart: Stock or other ownership interests: Cancer Centre London LLP; Consulting or advisory role: MSD, Roche, Bristol-Myers Squibb; Speaker’s bureau: Roche, Elekta; Research funding: MSD, Elekta; Travel expenses: Roche, MSD. All other authors have declared no conflicts of interest.