2522 - Apalutamide (APA) and Overall Survival (OS) in Patients (pts) With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results From the Phase 3 SPARTAN Study

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.