(UPDATE) Apalutamide in Prostate Cancer
Updated: Friday, September 3, 2021
Posted: Wednesday, July 18, 2018
Commentary by Sandy Srinivas, MD, Prostate Cancer Site Editor for JNCCN 360
Professor of Medicine, Stanford University Medical Center
The earlier use of androgen-receptor–targeted agents has resulted in a meaningful delay of radiographic disease progression, as well as improved overall survival in both hormone-sensitive prostate cancer and non-metastatic castration-resistant disease. In addition, these agents have been associated with improved quality of life. Androgen deprivation-therapy (ADT) intensification is the preferred treatment for patients with prostate cancer in several settings and is endorsed by the NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer.1
Dr. Srinivas has received clinical research support from or served on a data safety monitoring board for AstraZeneca, Bayer HealthCare, Bristol Myers Squibb, Clovis Oncology, Eisai, Exelixis, Genentech, Merck, Pfizer, Seattle Genetics, and Tracon Pharmaceuticals and has served on a scientific advisory board or as a consultant or expert witness for Bayer HealthCare, Eisai, Genentech, Janssen, and Merck.
Since the 2018 approval of apalutamide for patients with non-metastatic castration-resistant prostate cancer, the U.S. Food and Drug Administration (FDA) has also approved apalutamide for patients with metastatic castration-sensitive prostate cancer.2 This approval, granted on September 17, 2019, was based on results from the double-blind phase III TITAN study of more than 1,000 patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy (ADT), in which apalutamide added to ADT significantly improved overall and radiographic progression-free survival compared with ADT and placebo.3
The final analysis of TITAN, reported recently at the 2021 Genitourinary Cancers Symposium,4 confirmed that, despite crossover from placebo to apalutamide (allowed after study unblinding in January 2019), apalutamide in combination with ADT “improved overall survival, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with metastatic castration-sensitive prostate cancer.” With a median follow-up of 44 months, the researchers reported that apalutamide reduced the risk of death by 35% when compared with placebo plus ADT.
Additionally, longer follow-up of the double-blind phase III SPARTAN study, which led to the initial 2018 approval of apalutamide for non-metastatic castration-resistant prostate cancer, has also yielded new data.5 The final analysis showed that apalutamide significantly prolonged overall survival compared with placebo in patients with non-metastatic castration-resistant prostate cancer and prostate-specific antigen (PSA) doubling time of ≤ 10 months. Safety was consistent with previous reports.
At the SPARTAN trial’s primary analysis, overall survival data were not yet mature. However, data at that time showed that apalutamide significantly prolonged metastasis-free survival, with a median of 40.5 months compared with 16.2 months with placebo.6
- Schaeffer E, Srinivas S, Armstrong AJ, et al. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 2.2021—February 17, 2021. Accessed August 24, 2021. To view the most recent version of these guidelines visit NCCN.org.
- FDA approves apalutamide for metastatic castration-sensitive prostate cancer. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-apalutamide-metastatic-castration-sensitive-prostate-cancer. Accessed August 19, 2021.
- Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.
- Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol 2021;39:2294–2303.
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol 2021;79:150–158.
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378:1408–1418.