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2019 ASCO: TITAN Study Assesses Apalutamide vs Placebo During Androgen-Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer

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Key Points

  • Apalutamide improved radiographic progression-free survival, with a 52% reduction in risk of death or radiographic progression; benefit was observed across all subgroups analyzed.
  • Apalutamide also improved overall survival, with a 33% reduction in risk of death.
  • Rates of grade 3/4 adverse events were similar—42% in the apalutamide group and 41% in the placebo group. Treatment discontinuation due to adverse events was also low—8% in the apalutamide group and 5% in the placebo group.

Results from the phase III TITAN trial, presented by Chi et al at the 2019 ASCO Annual Meeting (Abstract 5006), showed that the addition of apalutamide to androgen-deprivation therapy (ADT) improved radiographic progression-free and overall survival in patients with metastatic castration-sensitive prostate cancer.

Study Background

In the randomized, double-blind, phase III study, patients were randomly assigned 1:1 (regardless of extent of disease) to apalutamide at 240 mg/d or placebo, added to ADT, in 28-day cycles. Patients with prior treatment for localized disease or prior docetaxel for metastatic castration-sensitive prostate cancer were allowed, and all patients received continuous ADT.

The median age was 68 years; 8% of patients had prior treatment(s) for localized disease; 11% had received prior docetaxel; and 63% and 37% had high- or low-volume disease, respectively. The primary endpoints were radiographic progression-free and overall survival.

Findings

At 22.6-month follow-up, 66% of patients in the apalutamide group and 46% of patients in the placebo group remained on treatment.

Apalutamide improved radiographic progression-free survival (hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.39–0.60; P < .0001), with a 52% reduction in risk of death or radiographic progression; that benefit was observed across all subgroups analyzed. The median radiographic progression-free survival was not reached in the apalutamide group and was 22.1 months in the placebo group.

Apalutamide also improved overall survival (HR = 0.67, 95% CI = 0.51–0.89; P = .0053), with a 33% reduction in risk of death. Median overall survival was not reached in the apalutamide or placebo groups. In addition, time to initiation of cytotoxic chemotherapy was significantly improved with apalutamide (HR = 0.39, 95% CI = 0.27–0.56; P < .0001). Based on these results, the independent data monitoring committee recommended unblinding to allow crossover of patients receiving placebo to receive apalutamide.

Rates of grade 3/4 adverse events were similar—42% in the apalutamide group and 41% in the placebo group. Treatment discontinuation due to adverse events was also low—8% in the apalutamide group and 5% in the placebo group.

The investigators concluded, “In the TITAN study in patients with metastatic castration-sensitive prostate cancer, including patients with high- and low-volume disease and prior docetaxel, addition of apalutamide to ADT significantly improved [radiographic progression-free survival] and [overall survival], and the safety profile was tolerable. These results support the addition of apalutamide to ADT for [the] treatment of patients with metastatic castration-sensitive prostate cancer.”

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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