The addition of apalutamide to androgen deprivation therapy (ADT) prolonged overall survival (OS) vs ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC), according to the results of the final analysis of the phase 3 TITAN trial. These findings, derived from nearly 4 years of follow-up, were presented at the 2021 Genitourinary Cancers Symposium.

“In addition, there was consistent benefit with apalutamide in other end points, including delaying castration resistance, and health-related quality of life continued to be maintained with an acceptable safety profile,” Kim N. Chi, MD, FRCPC, who presented the data.

In the phase 3 TITAN trial (NCT02489318), 1052 patients with mCSPC were randomly assigned to receive apalutamide plus ADT or ADT alone. Patients were eligible to enroll regardless of their volume of disease, and whether they’d received prior docetaxel or ADT or prior treatment for localized disease. The co-primary end points were OS and radiographic progression-free survival (rPFS).


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The first interim analysis, conducted at a median follow-up of 22.7 months, demonstrated that apalutamide significantly prolonged OS (HR, 0.67) and rPFS (HR, 0.48) compared with placebo. The trial was unblinded; as such, patients in the placebo group who did not have disease progression were permitted to crossover to receive apalutamide.

In this final analysis, a preplanned sensitivity analysis for OS was conducted, with crossover accounted for by inverse probability censoring weighted log-rank test. The median treatment duration was 39.3 months for the apalutamide plus ADT group, 20.2 months for the ADT alone group, and 15.4 months for the crossover group.

Nearly 40% (39.5%) of patients in the placebo arm crossed over to receive apalutamide. There were 525 patients in the combination therapy arm and 527 patients in the ADT arm.

OS was significantly prolonged with apalutamide, with a median of not estimable compared with 52.2 months with placebo after a median of 44 months of follow-up (HR, 0.65; P <.0001). This translated to a 48-month OS of 65% with apalutamide vs 52% with placebo.

When the analysis was adjusted for crossover, the HR further improved to 0.52 (P <.0001). Apalutamide was also found to prolong the time to castration resistance (HR, 0.34; P <.0001) and PFS2 (HR, 0.66; P <.0001).

“With close to 4 years of follow-up, the final analysis of TITAN demonstrated that in a broad population of patients with mCSPC, apalutamide plus ADT provides an improvement in OS with a 35% reduction in risk of death, which increased to 48% reduction after adjusting for patients who crossed over from placebo to apalutamide,” Chi concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by Janssen Research & Development.

Reference

Chi KN, Chowdhury S, Bjartell A, et al. Final analysis results from TITAN: A phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts)with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT). Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 11.

This article originally appeared on Cancer Therapy Advisor