ASCO GU 2020: Apalutamide for mCSPC in TITAN: Outcomes in Patients with Low- and High-Risk Disease

San Francisco, California (UroToday.com) Historically, androgen deprivation therapy (ADT) has been a standard of care for patients with metastatic castration sensitive prostate cancer (mCSPC). Apalutamide, an oral nonsteroidal androgen receptor inhibitor, binds directly to the ligand-binding domain of the androgen receptor, preventing the androgen receptors nuclear translocation and DNA binding and impeding androgen receptor-mediated transcription. The phase III TITAN study showed that apalutamide plus ADT improves radiographic progression-free survival (rPFS) and overall survival (OS) in a broad group of patients with mCSPC.¹ At the prostate cancer session at GU ASCO 2020, Mustafa Ozguroglu and colleagues presented results of their hoc analysis evaluating apalutamide plus ADT based on baseline prognostic risk as defined in LATITUDE study.²

TITAN included 1,052 patients with mCSPC that received ADT and were randomized 1:1 to apalutamide (240 mg/d; n = 525) or placebo (n = 527). Treatment cycles were 28 days. Risk included Gleason score ≥ 8, ≥ 3 bone lesions, or visceral metastasis. High risk was ≥ 2 risk factors, low risk was ≤ 1. Second progression free survival (PFS2) was analyzed as the time from randomization to progression on first subsequent therapy. Cox proportional hazards model was used to estimate HR and 95% CI for rPFS, OS and PFS2.

Patient demographics and baseline disease characteristics were similar between treatment groups (high risk: apalutamide n = 289, placebo n = 286; low risk: apalutamide n = 236, placebo n = 241). The median treatment duration was also similar in the low-risk group with apalutamide or placebo (21.8 months and 20.3 months, respectively). For the high-risk groups, treatment duration was longer with apalutamide (19.5 months) than with the placebo (14.7 months). First, subsequent therapies following discontinuation of the TITAN study treatment included abiraterone acetate plus prednisone and most commonly docetaxel. Apalutamide statistically significantly reduced the risk of radiographic progression relative to placebo in both groups:

The survival rates at 24 months were as follows: high risk 76% with apalutamide, high risk 63% with placebo, low risk 90% with apalutamide, and low risk 85% with placebo. Risk of death (OS) was reduced by 38% in high-risk pts and 26% in low-risk pts with APA:

However, there were a few deaths (≤ 33) in low-risk groups. The PFS2 also favored patients receiving apalutamide: high risk HR 1.9 (95% CI 1.2-3.0), p = 0.004; low risk HR 2.2 (95% CI 1.5-3.2), p < 0.0001:

Regardless of the risk category, the safety profile of APA remained consistent with previously reported overall results.

This post-hoc report of the TITAN study concluded with several key summary points:

Addition of apalutamide to ADT for patients with mCSPC prolonged rPFS and OS with a consistent safety profile compared with placebo plus ADT regardless of baseline risk
Patients who were considered high-risk at baseline had significantly improved OS following treatment with apalutamide
Treatment with apalutamide reduced the risk of PFS2 compared to placebo by 38% in the high-risk group and 31% in the low-risk group
The safety profile of apalutamide in both the high- and low-risk groups was consistent with previously published data

Clinical trial information: NCT02489318

Presented by: Mustafa Ozguroglu, MD, Professor of Medical Oncology, Istanbul University, Istanbul Turkey

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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