ESMO 2021: Apalutamide for Advanced Prostate Cancer in Older Patients: Combined Analysis of TITAN & SPARTAN

( The European Society of Medical Oncology (ESMO) 2021 annual meeting’s prostate cancer session included a presentation by Dr. John Shen discussing apalutamide for advanced prostate cancer in older patients. In TITAN and SPARTAN, apalutamide added to continuous androgen deprivation therapy (ADT) improved PSA response, radiographic progression-free survival (rPFS), metastasis-free survival (MFS), and overall survival (OS) in patients with metastatic castration-sensitive prostate cancer (mCSPC)1 and nonmetastatic castration-resistant prostate cancer (nmCRPC).2,3 The objective of this analysis presented at the ESMO 2021 meeting was to assess the efficacy and safety of apalutamide in the TITAN and SPARTAN studies by patient age.

In this study, mCSPC and nmCRPC patients were randomized 1:1 and 2:1 to receive apalutamide (240 mg QD) or placebo plus ADT, and placebo-to-apalutamide crossover after first interim analysis was 39.5% and 19%, respectively. In this post hoc analysis, patients were stratified by age: < 65 versus 65-79 versus ≥ 80 years. Time-to-event endpoints were analyzed by Kaplan-Meier method and Cox proportional hazards model:

  • rPFS and MFS at first interim analysis (TITAN: 22.7 months, SPARTAN: 20.3 months median follow-up)
  • PSA ≥ 50% decrease from baseline (PSA50)
  • OS 

Health-related quality of life per Functional Assessment of Cancer Therapy-Prostate was analyzed at the final analysis (TITAN: 44 months, SPARTAN: 52 months median follow-up).

There were 1,052 mCSPC (525 apalutamide, 527 placebo), and 1,207 nmCRPC (806 apalutamide, 401 placebo) patients assessed. Apalutamide added to ADT improved PSA50 in all age groups:

TITAN and SPARTAN-0.jpg 

Hazard ratios for rPFS favored apalutamide in all age groups in TITAN, with pronounced benefit in patients aged <65 and 65-79 years of age. MFS was also improved with apalutamide in patients of all ages:

TITAN and SPARTAN-1.jpg 

Hazard ratios for overall survival favored apalutamide across all groups, with pronounced benefit in patients <65 and 65-79 years of age in TITAN, and in patients <65 years of age in SPARTAN: 

TITAN and SPARTAN-2.jpg 

Health-related quality of life was maintained regardless of age or treatment group, with low side effect burden. In both studies, exposure-adjusted rates of adverse events leading to treatment discontinuation, falls, and ischemic heart disease was increased with age regardless of treatment, and rates of skin rash were increased with age in the apalutamide groups. 

Dr. Shen concluded his presentation assessing apalutamide stratified by age among patients in SPARTAN and TITAN with the following take-home messages:

  • Patients with mCSPC and nmCRPC derived clinical benefit and maintained HRQoL from apalutamide plus ADT regardless of age
  • Despite increased adverse event rates with age, patients did not report greater side effects bother with the addition of apalutamide to ADT
  • Age-related benefit/risk assessments should be taken into consideration in patients with advanced disease

Presented by: John Shen, MD, Department of Gastrointestinal Medical Oncology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.


  1. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 2019 Jul 4;381(1):13-24.
  2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
  3. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158.
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