Introduction:

In the phase 3 SPARTAN and TITAN studies in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-sensitive prostate cancer (mCSPC), respectively, addition of apalutamide to androgen deprivation therapy (ADT) significantly improved overall survival and other efficacy end points (Smith Eur Urol 2020; Chi NEJM 2019, and Chi J Clin Oncol 2021). In both studies, health-related quality of life was preserved with the addition of apalutamide to ADT. We evaluated the impact of the addition of apalutamide to ADT on sexual and urinary function.

Methods:

In SPARTAN, 1207 patients were randomized 2:1 to apalutamide (240 mg QD) or placebo (PBO), and in TITAN 1052 patients 1:1 to apalutamide (240 mg QD) or PBO in 28-day cycles; all patients received ADT. Sexual and urinary function were assessed by the responses to individual items on Functional Assessment of Cancer Therapy-Prostate (FACT-P). In SPARTAN, FACT-P was completed pre-dose on Day 1 of: Cycles 1-6, every 2 cycles from 7 to 13, every 4 cycles thereafter, at the end of treatment (EOT), and every 4 months post progression for up to 1 year. In TITAN, FACT-P was assessed at Cycles 1-7, every other cycle starting from Cycle 8 to EOT, and at 4, 8, and 12 months of follow-up. Descriptive statistics are reported. Findings include mean scores over time between groups and stratified by baseline function level.

Results:

Median follow-up was 52 months for SPARTAN and 44 months for TITAN. At each cycle, FACT-P questionnaires were completed by ≥ 96% of eligible SPARTAN patients through Cycle 33 and by ≥ 51% of eligible TITAN patients through Cycle 31 (> 75% through Cycle 25). At baseline, 85% of patients across both studies reported inability to maintain erections, and ~4 of 5 patients reported difficulty urinating and activity limitations due to urinary problems. For patients with favorable function at baseline, symptoms worsened at first postbaseline assessment, regardless of treatment, and remained stable thereafter; there were no differences between apalutamide and PBO groups.

Conclusion:

Most patients with nmCRPC (SPARTAN) and mCSPC (TITAN) experienced erectile dysfunction and urinary symptoms prior to initiating study treatment. In the final analyses of these studies, sexual and urinary function remained stable over time with addition of apalutamide to ADT.

Funding: Janssen Research & Development