Moderator: Solange Peters, ESMO 2014 Press Officer - Speakers: Rolf Stahel, ESMO President; Johann de Bono, ESMO 2014 Scientific Chair

Breast Cancer: Evandro de Azambuja , GI-Cancer: Dirk Arnold, Lung Cancer: Stefan Zimmermann, GUN-Cancer: Markus Joerger, Melanoma: Ulrich Keilholz

The future of ESMO:

Rolf A.Stahel, University Hospital Zürich, Switzerland:

   

Top practice changes to implement after ESMO 2014

Johann de Bono, Royal Marsden Hospital and The Institute of Cancer Research, United Kingdom:

   

What’s in the pipeline

GUN-Cancer: Markus Joerger, Breast Cancer: Evandro de Azambuja, GI-Cancer: Dirk Arnold, Lung Cancer: Stefan Zimmermann, Melanoma: Ulrich Keilholz:

   

FINAL OVERALL SURVIVAL (OS) ANALYSIS OF COU-AA-302,

A RANDOMIZED PHASE 3 STUDY OF ABIRATERONE ACETATE (AA) IN METASTATIC CASTRATIONRESISTANT PROSTATE CANCER (MCRPC) PATIENTS (PTS) WITHOUT PRIOR CHEMOTHERAPY

C.J. Ryan, M.R. Smith, K. Fizazi, K. Miller, et al.: (FULL TEXT)

Aim

AA is a prodrug of abiraterone, a selective CYP17 inhibitor that blocks androgen biosynthesis and is approved, with prednisone (P), for the treatment of pts with progressive mCRPC. Planned interim analyses of COU-AA-302 (at 13%, 43%, and 56% death events) in mCRPC chemotherapy-naïve pts showed that AA + P significantly delayed disease progression and improved OS compared with P alone, and was well tolerated.1,2 Herein, we report the pre-specified final analysis (96% of planned death events) OS and safety outcomes.

Methods

Pts (N = 1088) were randomized 1:1 to receive AA (1 g) + P (5 mg po BID) vs P. Co-primary end points were radiographic progression-free survival and OS. Median time to events with 95% CI was estimated using the Kaplan-Meier method. Cox model was used to estimate the hazard ratio (HR). Stratified log-rank test was used to test the difference in treatment effect. The O'Brien-Fleming boundary using the Lan-DeMets •-spending function was implemented to control the overall • at 0.04 for OS. For this final analysis, the nominal significance level for efficacy is 0.0384.

Results

With median follow-up of 49.4 mos at final analysis, 741 deaths were observed. 44% of pts in the P arm subsequently received AA + P. AA + P significantly prolonged OS vs P (median OS, 34.7 vs 30.3 mos; HR = 0.80 [95% CI, 0.69-0.93]; p = 0.0027). AEs of special interest were more common with AA + P vs P; grade 3/4 AEs: hypertension, 4.6% vs 3.1%; hypokalemia, 2.6% vs 1.9%; ALT increased, 5.9% vs 0.7%; AST increased, 3.3% vs 0.9%; fluid retention/edema, 1.1% vs 1.7%.

Conclusions

With a median follow-up of more than 4 years, the COU-AA-302 pre-specified, final analysis demonstrates a statistically significant OS benefit with AA + P even though a large number of pts in the P arm received AA + P and other subsequent therapy. With nearly an additional 2 years of follow-up since last reported, AA + P maintains a favorable safety profile and is well tolerated.

1. Ryan CJ et al. NEJM. 2013;368:138-148.

2. Rathkopf DE et al. Eur Urol. 2014 March 6 [Epub ahead of print].