ASCO GU 2019: Updated Analysis of Progression-Free Survival with First Subsequent Therapy and Safety in the SPARTAN Study of Apalutamide in Patients with High-Risk nmCRPC

San Francisco, CA ( Apalutamide is a nonsteroidal androgen receptor inhibitor which directly binds to the ligand binding domain of the androgen receptor and prevents AR translocation, DNA binding, and AR-mediated transcription.1 Based on the results of SPARTAN, a double-blind placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer with a PSA doubling time of 10 months or less, the FDA approved apalutamide in February of 2018 for non-metastatic CRPC. In this study, a total of 1207 men underwent randomization to apalutamide or placebo and at the time of primary analysis, the median metastasis-free survival was 40.5 months in the apalutamide group compared with 16.2 months in the placebo group. The time to symptomatic progression was also longer with apalutamide (HR 0.45), and about 11% of patients in the apalutamide group discontinued the drug due to side effects. Fatigue and rash were two of the most common side effects, affecting 30.4% and 24% of patients on this study respectively. This study provides an update to the analysis of PFS data.
After an additional year of follow up, the authors here provide updated safety and PFS data on the 1207 men with nmCRPC with PSA doubling time <10 months who were randomized to receive apalutamide or placebo. Upon initial progression, patients had the option to receive open-label treatment with abiraterone provided by the sponsor. At the time of this report, the median treatment duration on apalutamide was 25.7 months and 11.5 months on placebo. In terms of safety, no new safety signals have been observed. Notable grade 3 treatment-emergent adverse events included rash (5.2%), falls (2.4%), and fractures (3.1%).  412 patients have discontinued apalutamide thus far. The most common reason was progressive disease (53%), followed by adverse events (25%), and withdrawal by patient (16%). 
An important endpoint described here was PFS2, the timefrom randomization to time to disease progression on the subsequent therapy. Median time of progression on subsequent therapy after apalutamide was not yet reached, compared to 39.3 months for patients initially randomized to placebo (HR, 0.5; 95% CI, 0.390.63; p < 0.0001).

Apalutamide continues to show benefit for patients with nmCRPC, not only for increasing metastasis-free survival, but also for increasing PFS2, with a favorable side effect profile. With data coming out this GU ASCO on darolutamide, there will soon be three options (enzalutamide, apalutamide, darolutamide) for patients with nmCRPC and patient factors will be important to consider which is the best-personalized option.
APA PFS2 Improvement ASCO GU

Presented by: Eric J. Small, MD, FASCO, UCSF Helen Diller Family Comprehensive Cancer Care Center 
Discussant: Nicholas J. van As, MBBCH, MRCP, FRCR, MD(res), Institute of Cancer Research and The Royal Marsden NHS Foundation Trust

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

  1. Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. New England Journal of Medicine 2018;378:1408-18.