Pivotal long-term data published for apalutamide in mCSPC

Adding apalutamide (Erleada) to androgen-deprivation therapy (ADT) reduced the risk of death by 35% versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC), according to long-term outcomes from the final analysis of the pivotal phase 3 TITAN trial published in the Journal of Clinical Oncology.1 

The results, which were previously shared during the 2021 Genitourinary Cancers Symposium, showed that at a median follow-up of 44.0 months, the median overall survival (OS) was not reached in the apalutamide arm compared with 52.2 months in the control arm (HR, 0.65; P <.0001). After adjusting for crossover using a preplanned sensitivity analysis, investigators found a 48% reduction in the risk of death (HR, 0.52; P <.0001).

“The final analysis of TITAN demonstrated that the long-term use of apalutamide plus ADT provided significant improvement in overall survival and delayed onset of progression despite almost 40% crossover from placebo to apalutamide after the study was unblinded,” lead study author Kim N. Chi, MD, chief medical officer and vice president of BC Cancer, Vancouver, Canada, and coauthors wrote.

“With substantially longer follow-up and exposure than at the primary analysis, apalutamide treatment had a safety profile consistent with previous reports and patients maintained health-related quality of life under treatment with apalutamide,” added Chi et al.

The TITAN trial (NCT02489318) randomized 1052 patients with mCSPC in a 1:1 ratio to receive apalutamide plus ADT or placebo plus ADT. The dual primary end points were radiographic progression-free survival (rPFS) and OS.

The previously published primary analysis of the trial showed that at a median follow-up of 22.7 months, a statistically significant benefit in both rPFS and OS was achieved with the apalutamide combination.2 This initial analysis showed 2-year OS rates of 82.4% in the apalutamide arm compared with 73.5% in the control arm, translating to a 33% reduction in the risk of death (HR, 0.67; P = .005).

At the primary analysis the trial was unblinded based on the recommendation of the independent data monitoring committee. At this point, 39.5% of patients in the placebo group who had not progressed went on to receive open-label apalutamide.

The safety profile at the primary analysis showed that adverse events occurring in ≥10% of patients receiving apalutamide included fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.3

Based on the efficacy and safety data from the primary TITAN analysis, the FDA approved apalutamide in September 2019 for the treatment of patients with mCSPC.

In their concluding remarks, Chi et al wrote that the final TITAN analysis confirms that, “Patients with mCSPC can benefit from early treatment intensification with the addition of apalutamide to ADT.”


1. 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 [published online ahead of print April 29, 2021]. J Clin Oncol. doi: 10.1200/JCO.20.03488

2. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24. doi:10.1056/NEJMoa1903307

3. FDA approves apalutamide for metastatic castration-sensitive prostate cancer. Last updated September 18, 2019. Accessed May 6, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-apalutamide-metastatic-castration-sensitive-prostate-cancer