AUA 2020: Apalutamide for Metastatic Castration-Sensitive Prostate Cancer in TITAN: Prognostic Importance of Prostate-Specific Antigen Responses

(UroToday.com) Apalutamide is an oral non-steroidal anti-androgen agent that binds to the androgen receptor and prevents nuclear translocation, DNA binding, and androgen receptor-mediated transcription.

In the phase three TITAN study, it was shown that apalutamide plus ADT significantly improved overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression in a broad population of patients who had metastatic hormone-sensitive prostate cancer.1

This presentation is a post hoc analysis of the TITAN study that evaluated PSA declines in associations with clinical outcomes.

The study design of TITAN is shown in Figure 1. The TITAN study demonstrated that the rates of both radiographic progression-free survival and overall survival were significantly improved in patients treated with apalutamide plus ADT versus those treated with placebo plus ADT (Figure 2).

Figure 1 – TITAN study design:

TITANStudyDesign_AUA2020.png

Figure 2 – Radiographic progression-free survival and overall survival in the TITAN study:

RPFS_Figure2_AUA2020.png

In the TITAN study, a total of 1052 patients with metastatic hormone-sensitive prostate cancer receiving ADT were randomized one to one to either apalutamide or placebo with a median follow-up time of 22.7 months. The depth of PSA response was evaluated by categorizing patients with PSA decline to <=0.2 ng/ml or decline by <50%, >=50-90%, or >=90% from baseline. The time to castration resistance was defined as the time to PSA progression, or skeletal-related event, or radiographic progression, whichever came first. Overall survival was defined as the time from randomization to the date of death from any cause. Lastly, radiographic progression-free survival was defined as the time from randomization to the first documentation of radiographic progressive disease or death, whichever came first.

Table 1 Demonstrates the depth of PSA response that was superior with apalutamide compared to that with placebo.

Table 1- Depth of PSA response with apalutamide compared to placebo:

Table1_DepthofPSAResposne_AUA2020.png

Importantly, more patients in the apalutamide group compared to the placebo group achieved PSA responses over time, as can be seen in Table 2.

Table 2 – PSA responses over time in the TITAN study:

PSAResponseOvertime_AUA2020.png

In patients treated with apalutamide, PSA response was associated with improved radiographic progression-free survival, overall survival, and castration resistance. Patients who achieved PSA response following three months of apalutamide treatment also had improved overall survival, radiographic progression-free survival, and time to castration resistance, as seen in Figures 3, 4, and 5, respectively.

Figure 3 – Overall survival stratified by PSA response:

OverallSurvival_Figure3_AUA202.png

Figure 4 – Radiographic progression-free survival stratified by PSA response:

rPFS_Figure4_AUA2020.png

Figure 5 – Time to castration resistance stratified by PSA response:

TimetoCastrationResistance_Figure5_AUA2020.png

In conclusion, treatment with apalutamide plus ADT demonstrated a robust response in serum PSA levels that were sustained over time in this unique population of patients with metastatic hormone-sensitive prostate cancer. The magnitude and depth of PSA response were associated with a significant extension and improvement of overall survival and a significant reduction and delay in radiographic progression-free survival, and the development of castration resistance. Lastly, the deep and rapid PSA response that was shown in patients treated with apalutamide plus ADT, as early as three months, was associated with significantly improved long term clinical outcomes indicating a prognostic impact.

Presented by: Simon Chowdhury, MD, Consultant Medical Oncologist, The London Clinic, London, UK

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.

References:

  1. Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. New England Journal of Medicine. 2019;381(1):13-24.
Related Content: 

Read: Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. 
Watch: Patient-reported Outcomes from TITAN: Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer - Neeraj Agarwal

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