Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Apalutamide and Overall Survival in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: Updated Results From the Phase 3 SPARTAN Study (#194)

Thean Hsiang Tan 1 , Matthew R Smith 2 , Saad Fred 3 , Simon Chowdhury 4 , Stéphane Oudard 5 , Boris A Hadaschik 6 , Julie N Graff 7 , David Olmos 8 , Paul N Mainwaring 9 , Ji Youl Lee 10 , Hiroji Uemura 11 , Peter De Porre 12 , Andressa Smith 13 , Ke Zhang 14 , Angela Lopez-Gitlitz 15 , Eric J Small 16
  1. Royal Adelaide Hospital, Adelaide, SA, Australia
  2. General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA
  3. Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Québec, Canada
  4. Guy’s, King’s and St. Thomas’ Hospitals, and Sarah Cannon Research Institute, London, UK
  5. Georges Pompidou Hospital, Paris, France
  6. University of Duisburg-Essen, Essen, and Ruprecht-Karls University Heidelberg, Heidelberg, Germany
  7. Portland and Knight Cancer Institute, Oregon Health & Science University, Portland, USA
  8. Spanish National Cancer Research Centre (CNIO), Madrid and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga , Spain
  9. Centre for Personalized Nanomedicine, University of Queensland, Brisbane, Australia
  10. St. Mary’s Hospital of Catholic University, Seoul, South Korea
  11. Yokohama City University Medical Center, , Yokohama, Japan
  12. Janssen Research & Development, Beerse, Belgium
  13. Janssen Research & Development, Spring House, PA, USA
  14. Janssen Research & Development, San Diego, CA, USA
  15. Janssen Research & Development, Los Angeles, CA, USA
  16. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

Background: In the phase 3 placebo-controlled SPARTAN study, apalutamide with ongoing androgen deprivation therapy (ADT) significantly improved metastasis-free-survival (MFS) (HR,0.28;95% CI, 0.23-0.35; p<0.001), time to symptomatic progression, and progression-free survival on second therapy vs. PBO with ongoing ADT in patients with nmCRPC. At the primary analysis for MFS, apalutamide was associated with improved OS (HR,0.70;95% CI,0.47-1.04; p=0.07) and time to initiation of cytotoxic chemotherapy. OS results were immature, with only 104 of 427 events (24%) required for the prespecified final OS analysis. We report a second interim analysis (IA2). Methods: Patients with nmCRPC and prostate-specific antigen doubling time of ≤ 10 months were randomized 2:1 to apalutamide (240 mg QD) or placebo, with ongoing ADT. The OS effect of apalutamide vs. placebo was assessed using a group sequential testing procedure with O’Brien-Fleming-type alpha spending function. The required p-value for statistical significance at IA2 was 0.0121. OS was analyzed by Kaplan-Meier method and Cox model. Results: At 41 months’ median follow-up and 285 OS events, apalutamide was associated with 25% OS compared with placebo. The 4-yr OS rates for apalutamide and placebo were 72.1% and 64.7%, respectively. After unblinding and prior to IA2, 19% placebo patients crossed over to open-label apalutamide. At IA2, the proportion of patients who received subsequent life-prolonging therapy was 68% in the placebo group and 38% in the apalutamide group. Rates of discontinuation due to progressive disease and adverse events (AE) were 34% and 14%, for the apalutamide group, and 74% and 8% for the placebo group. Conclusions: At IA2, apalutamide was associated with a 25% reduction in risk of death vs. placebo. OS benefit for apalutamide was observed despite crossover of placebo patients to apalutamide and higher rates of subsequent life-prolonging therapy for placebo patients. apalutamide safety profile remained unchanged. These results support apalutamide as a standard of care option for patients with high-risk nmCRPC.