A randomized phase III study comparing paclitaxel-BEP (T-BEP) to standard BEP in patients with in intermediate prognosis germ cell cancer (GCC): An intergroup study of EORTC, German TCSG/AUO, MRC, and Spanish GCC group (EORTC 30983).

Abstract

4509 Background: To compare the efficacy of 4 cycles of T-BEP to 4 cycles of BEP in previously untreated patients (pts) with intermediate prognosis GCC. Methods: Pts were randomly assigned to receive either standard BEP (cisplatin 20 mg/m2 d1-5, etoposide100 mg/m2 d1-5, bleomycin 30 mg weekly) or T-BEP (paclitaxel 175 mg/m2 given as a 3-hours infusion on d1, before starting standard BEP. Pts on T-BEP received primary G-CSF prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year PFS (2-sided Logrank, α= 5%, 80% power), the study needed 498 patients (98 events planned), but closed with 337 due to slow accrual. Primary analysis is by intent-to-treat (ITT) at α=0.0455 (adjusted for interim). ClinicalTrials.gov id: NCT00003643. Results: Accrual was from 11/1998 to 04/2009. 169 pts were assigned BEP and 168 T-BEP. 13 pts on both arms were ineligible, mainly due to good prognosis GCC (8 on BEP, 6 on T-BEP). Of 5 pts ineligible due to poor risk GCC, 4 had been allocated T-BEP. Relative dose-intensity was > 97.7% for all drugs. T-BEP was well tolerated; 31 episodes of neutropenic fevers were reported on T-BEP (compared to 18 on BEP), but there were only 2 toxic deaths. After a median follow-up of 5.3 years, a total of 84 events occurred. PFS at 3-years (ITT) was 79.4% on T-BEP versus 71.1% on BEP, HR= 0.73 (CI: 0.47-1.13), logrank P = 0.153. PFS at 3-years in all eligible pts was 82.7% versus 70.1%, respectively, HR=0.60 (CI: 0.37-0.97) and statistically significant, logrank P = 0.03. Overall survival was not statistically different. Conclusions: The PFS intent-to-treat (primary efficacy) analysis is not statistically significant, but is negatively influenced by the uneven distribution of ineligible pts amongst the 2 treatment arms. The analysis of all eligible pts, however, shows a 12% superior 3-year PFS with T-BEP, which is statistically significant. This study demonstrates superior efficacy of T-BEP in the management of the intended intermediate prognosis GCC risk group. This is the first study to show superiority over standard BEP in this population.