1910 - Patient-Reported Outcomes (PROs) From TITAN: a Phase 3, Randomized, Double-Blind Study of Apalutamide (APA) Versus Placebo (PBO) Added to Androgen Deprivation Therapy (ADT) in Patients (pts) With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Background

Compared with PBO, addition of APA to ADT significantly improved radiographic progression-free survival (rPFS [HR, 0.48; 95% CI, 0.39-0.60; p < 0.0001]), and overall survival (OS [HR, 0.67; 95% CI, 0.51-0.89; p = 0.0053]) in pts with mCSPC (TITAN Study; Chi KN et al. NEJM 2019). In this analysis, we evaluated pain, fatigue, and overall health-related quality of life (HRQoL) of pts in TITAN.

Methods

mCSPC pts (N = 1052) were randomized 1:1 to APA (240 mg QD; n = 525) or PBO (n = 527). All pts received ADT. Pts were stratified by Gleason score at diagnosis (≤ 7 vs > 7), region (North America vs European Union vs other countries), and prior docetaxel use (yes vs no). PROs were assessed using the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Euro QoL Group EQ-5D-5L. BPI and BFI were completed for 7 consecutive days (D) (D -6 plus D1 of each cycle [C] visit), then at Months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed C1 through C7, then every other C through end of treatment (tmt), and at Months 4, 8, and 12 in follow-up. Analyses included descriptive statistics and mean change from baseline using mixed model of repeated measures.

Results

Pts were relatively asymptomatic at baseline: on 0-10 severity scales, median pain scores were 1.14 (APA) and 1.00 (PBO), and median fatigue scores were 1.29 (APA) and 1.43 (PBO). Pt experience of pain and fatigue (both intensity and interference) was similar between groups for the duration of tmt. For the majority of pts in both arms, pain and fatigue remained stable or improved during tmt, with greater improvements observed in pts with higher baseline severity scores. FACT-P total score and EQ-5D-5L data showed similar maintenance of overall HRQoL in both arms. Similar tolerability was experienced between groups based on the FACT-P single item side effects bother question.

Conclusions

The addition of APA to ADT maintained overall HRQoL while significantly improving OS and rPFS in mCSPC pts.

Clinical trial identification

NCT02489318.

Editorial acknowledgement

Chris R. Prostko, PhD, of Parexel.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

N. Agarwal: Advisory / Consultancy: Argos Therapeutics; AstraZeneca; Bayer; Bristol-Myers Squibb; Clovis Oncology; Eisai; EMD Serono; Exelixis; Foundation One Inc; Genentech/Roche; Lilly; Medivation/Astellas; Merck; Nektar; Novartis; Pfizer; Research grant / Funding (institution): Active Biotech; Amgen; AstraZeneca; Bavarian Nordic; Bayer; BN ImmunoTherapeutics; Bristol-Myers Squibb; Calithera Biosciences; Celldex; Eisai; Exelixis; Genentech; GlaxoSmithKline; Immunomedics; Janssen; Medivation; Merck; Newlink Genetics. K. McQuarrie: Full / Part-time employment: Janssen; Shareholder / Stockholder / Stock options: Johnson & Johnson. A. Bjartell: Shareholder / Stockholder / Stock options: Glactone Pharma AB. S. Chowdhury: Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self): Novartis; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Bayer; Advisory / Consultancy: Janssen-Cilag; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Research grant / Funding (institution): Sanofi/Aventis. B.H. Chung: Honoraria (self), Advisory / Consultancy: Astellas (Korea); Honoraria (self), Advisory / Consultancy: Ipsen (Korea); Honoraria (self): JW Pharma (Korea); Honoraria (self): Takeda (Korea); Advisory / Consultancy: Janssen (Korea); Advisory / Consultancy: Handok (Korea); Research grant / Funding (self): Janssen (USA); Research grant / Funding (self): Bayer (Germany); Research grant / Funding (self): Pfizer (USA); Research grant / Funding (self): AstraZeneca (UK). Juárez Soto: Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Coloplast; Research grant / Funding (self): Bayer. A. Merseburger: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas. H. Uemura: Honoraria (self), Travel / Accommodation / Expenses: Janssen; Honoraria (self): Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda; Honoraria (self), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: AstraZeneca. R. Given: Shareholder / Stockholder / Stock options: Multiple companies as individual stock and within mutual funds; Honoraria (self): HealthTronics; Speaker Bureau / Expert testimony, Research grant / Funding (self): Janssen; Research grant / Funding (self): Ferring; Research grant / Funding (self): Veru; Research grant / Funding (self): Medivation; Research grant / Funding (self): Clovis. B. Miladinovic: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. L. Dearden: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. K. Deprince: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. V. Naini: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. A. Lopez-Gitlitz: Full / Part-time employment: Janssen Research & Development; Shareholder / Stockholder / Stock options: Johnson & Johnson. K.N. Chi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: ESSA; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Lilly/ImClone; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tokai Pharmaceuticals. All other authors have declared no conflicts of interest.