(UPDATE) Apalutamide in Prostate Cancer

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

DISCLOSURES

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

References

1. 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.
2. 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.
3. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.
4. 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.
5. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol 2021;79:150–158.
6. 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.