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

Date

27 Sep 2019

Session

Proffered Paper – Genitourinary tumours, prostate

Presenters

Matthew Smith

Citation

Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248

Authors

M.R. Smith1, F. Saad2, S. Chowdhury3, S. Oudard4, B.A. Hadaschik5, J.N. Graff6, D. Olmos7, P.N. Mainwaring8, J.Y. Lee9, H. Uemura10, P. De Porre11, A. Smith12, K. Zhang13, A. Lopez-Gitlitz14, E.J. Small15

Author affiliations

  • 1 Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, 02114 - Boston/US
  • 2 Department D'urologie, Centre Hospitalier de l'Université de Montréal, Université de Montréal, H2X 0A9 - Montréal/CA
  • 3 Department Of Medical Oncology, Guy’s, King’s and St. Thomas’ Hospitals, and Sarah Cannon Research Institute, SE1 9RT - London/GB
  • 4 Department Of Medical Oncology, Georges Pompidou Hospital, 75015 - Paris/FR
  • 5 Department Of Urology, University of Duisburg-Essen, Essen, and Ruprecht-Karls University Heidelberg, Heidelberg/DE
  • 6 Department Of Hematology/oncology, VA Portland Health Care System, Portland and Knight Cancer Institute, Oregon Health & Science University, 97239 - Portland/US
  • 7 Department Of Cancer Clinical Research, Spanish National Cancer Research Centre (CNIO), Madrid and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga/ES
  • 8 Department Of Medical Oncology, Centre for Personalized Nanomedicine, University of Queensland, 4072 - Brisbane/AU
  • 9 Department Of Urology, St. Mary’s Hospital of Catholic University, Seoul/KR
  • 10 Department Of Urology And Renal Transplantation, Yokohama City University Medical Center, 232-0024 - Yokohama/JP
  • 11 Department Of Clinical Oncology, Janssen Research & Development, 2340 - Beerse/BE
  • 12 Department Of Clinical Oncology, Janssen Research & Development, Spring House/US
  • 13 Department Of Clinical Biostatistics, Janssen Research & Development, San Diego/US
  • 14 Department Of Clinical Oncology, Janssen Research & Development, Los Angeles/US
  • 15 Department Of Medicine/division Of Hematology/oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 94115 - San Francisco/US
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Background

In the phase 3 placebo (PBO)-controlled SPARTAN study, APA 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 compared with PBO with ongoing ADT in pts with nmCRPC. At the primary analysis for MFS, APA was associated with improved OS (HR, 0.70; 95% CI, 0.47-1.04; p = 0.07) and time to initiation of cytotoxic chemotherapy. The 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) for OS after 285 events (65% of required events).

Methods

Pts with nmCRPC and prostate-specific antigen doubling time of ≤ 10 months were randomized 2:1 to APA (240 mg QD) or PBO, with ongoing ADT. The OS effect of APA vs PBO 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, APA was associated with improved OS compared with PBO (HR, 0.75; 95% CI, 0.59-0.96; p = 0.0197). The 4-yr OS rates for APA and PBO were 72.1% and 64.7%, respectively. After unblinding the study and prior to IA2, 76 nonprogressing PBO pts (19%) crossed over to open-label APA. At IA2, the proportion of pts who received subsequent life-prolonging therapy was 68% in the PBO group and 38% in the APA group. Rates of discontinuation due to progressive disease and adverse events (AE) were 34% and 14%, for the APA group, and 74% and 8% for the PBO group. The rates of treatment-emergent AEs for APA at IA2 were similar to the rates previously reported at IA1.

Conclusions

At IA2, APA was associated with a 25% reduction in risk of death compared with PBO. This OS benefit for APA was observed despite crossover of PBO pts to APA and higher rates of subsequent life-prolonging therapy for PBO pts. APA safety profile remained unchanged. These results further support APA as a standard of care option for pts with high-risk nmCRPC.

Clinical trial identification

NCT01946204.

Editorial acknowledgement

William Turner, PAREXEL.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

M.R. Smith: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy, Research grant / Funding (self): Janssen Oncology; Advisory / Consultancy: Amgen; Advisory / Consultancy: Pfizer; Research grant / Funding (self): Gilead Sciences. F. Saad: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: AstraZeneca/Medimmune; Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Oncogenex. S. Chowdhury: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Johnson & Johnson; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Clovis. S. Oudard: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai. B.A. Hadaschik: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: Lightpoint Medical; Research grant / Funding (self): Profound Medical; Research grant / Funding (self): German Cancer Aid; Research grant / Funding (self): German Research Foundation; Travel / Accommodation / Expenses: AstraZeneca. J.N. Graff: Honoraria (self), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Exelixis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Travel / Accommodation / Expenses: Clovis Oncology; Licensing / Royalties: Oncoresponse: Exceptional responders; Honoraria (self): Astellas Medivation; Honoraria (self), Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Bristol-Myers Squibb. D. Olmos: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Clovis Oncology; Travel / Accommodation / Expenses: Ipsen; Honoraria (self): Sanofi; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Astellas Medivation; Research grant / Funding (institution): Tokai Pharmaceuticals. P.N. Mainwaring: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Pfizer; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen Oncology; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Medivation/Astellas; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Licensing / Royalties: 4 patents on nanotechnology; Shareholder / Stockholder / Stock options: Xing Technologies; Research grant / Funding (self): Merck KGaA. H. Uemura: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Sanofi; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Merck Sharp Dohme. P. De Porre: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. A. Smith: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. K. Zhang: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. A. Lopez-Gitlitz: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. E.J. Small: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Fortis; Advisory / Consultancy: Janssen Oncology; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Shareholder / Stockholder / Stock options: Harpoon Therapeutics. All other authors have declared no conflicts of interest.

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