Adding apalutamide to androgen deprivation therapy (ADT) significantly improved overall survival (OS) and delayed progression in patients with metastatic, castration-sensitive prostate cancer (mCSPC), according to final results of the TITAN study published in the Journal of Clinical Oncology.

The double-blind, phase 3 TITAN study ( Identifier: NCT02489318) enrolled 1052 patients with mCSPC who were randomly assigned to receive apalutamide plus ADT (525 patients) or placebo plus ADT (527 patients).

After the trial was unblinded, 208 patients (39.5%) from the placebo group crossed over to receive apalutamide.

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The median treatment duration was 15.4 months for the crossover group, 20.2 months for the placebo-ADT group, and 39.3 months for the apalutamide-ADT group.

With a median follow-up of 44.0 months, there were 405 deaths — 170 in the apalutamide arm and 235 in the placebo arm.

The risk of death decreased by 35% in patients treated with apalutamide (hazard ratio [HR], 0.65; 95% CI, 0.53-0.79; P <.0001). The median OS was not reached in the apalutamide arm and was 52.2 months in the placebo arm.

After adjustment for patient crossover, there was a 48% reduction in the risk of death with apalutamide (HR, 0.52; 95% CI, 0.42-0.64; P <.0001). The median OS was 39.8 months in the placebo arm and was not reached in the apalutamide arm.

In addition, apalutamide significantly delayed the time to prostate-specific antigen progression (HR, 0.27, 95% CI, 0.22-0.33; P <.0001), time to second progression-free survival (HR, 0.62; 95% CI, 0.51-0.75; P <.0001), and time to castration resistance (HR, 0.34; 95% CI, 0.29-0.41; P <.0001). 

Rash and fatigue were the most common adverse events associated with apalutamide. There were no treatment-related fatalities.

Three patients from the crossover group developed COVID-19. Treatment-emergent adverse events in these patients resolved and did not lead to treatment discontinuation or death.

With longer follow-up and exposure than in the primary analysis, apalutamide treatment maintained patients’ health-related quality of life and demonstrated an acceptable safety profile, according to the study authors.

“[T]he final analysis of TITAN and its long-term results demonstrate that apalutamide plus ADT consistently provides significant improvements in OS and delays the onset of progression despite a large number of placebo-treated patients crossing over to active treatment with apalutamide during the study,” the authors wrote. “These results support the early addition of apalutamide to ADT for optimal therapeutic outcomes in patients with mCSPC.”

Disclosures: This research was supported by Janssen Research & Development. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


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. Published online April 29, 2021. doi:10.1200/JCO.20.03488