2019 ASCO Annual Meeting!
Session: Genitourinary (Prostate) Cancer
Type: Oral Abstract Session
Time: Friday May 31, 2:45 PM to 5:45 PM
Location: Arie Crown Theater
First results from TITAN: A phase III double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT).
Genitourinary (Prostate) Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 5006)
Author(s): Kim N. Chi, Neeraj Agarwal, Anders Bjartell, Byung Ha Chung, Andrea Juliana Pereira de Santana Gomes, Robert W. Given, Álvaro Juárez Soto, Axel Stuart Merseburger, Mustafa Ozguroglu, Hirotsugu Uemura, Dingwei Ye, Kris Deprince, Vahid Naini, Jinhui Li, Shinta Cheng, Margaret K. Yu, Ke Zhang, Julie S. Larsen, Sharon Anne McCarthy, Simon Chowdhury; BC Cancer, Vancouver, BC, Canada; University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Skåne University Hospital, Lund University, Malmö, Sweden; Yonsei University College of Medicine and Gangnam Severance Hospital, Seoul, South Korea; Liga Norte Riograndense Contra O Cancer, Natal, Brazil; Urology of Virginia, Eastern Virginia Medical School, Norfolk, VA; Hospital Universitario de Jerez de la Frontera, Cadiz, Spain; University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey; Kindai University Faculty of Medicine, Osaka, Japan; Fudan University Shanghai Cancer Center, Shanghai, China; Janssen Research & Development, Beerse, Belgium; Janssen Research & Development, San Diego, CA; Janssen Research & Development, Raritan, NJ; Janssen Research & Development, Los Angeles, CA; Guy’s, King’s and St. Thomas’ Hospitals, and Sarah Cannon Research Institute, London, United Kingdom
Background: TITAN was designed to determine whether APA, a selective next-generation androgen receptor inhibitor, plus ADT improves radiographic progression-free survival (rPFS) and overall survival (OS) compared with PBO plus ADT in pts with mCSPC. Methods: In this randomized, double-blind phase 3 study, pts with mCSPC regardless of extent of disease were randomized (1:1) to APA (240 mg/d) or PBO, added to ADT, in 28-day cycles. Pts with prior treatment (tx) for localized disease or prior docetaxel for mCSPC were allowed. All pts received continuous ADT. Dual primary end points were rPFS and OS. Secondary end points were time to a) initiation of cytotoxic chemotherapy, b) pain progression, c) chronic opioid use, d) skeletal-related event. Time-to-event end points were estimated by Kaplan-Meier and Cox proportional hazards methods. This first planned OS interim analysis took place after ~50% of expected events. Results: 525 pts were randomized to APA and 527 to PBO. Median age was 68 y; 8% had prior tx for localized disease; 11% had prior docetaxel. 63% and 37% had high- or low-volume disease, respectively. At median 22.6 mo follow-up, 66% APA and 46% PBO pts remained on tx. APA significantly improved rPFS (HR, 0.48; 95% CI, 0.39-0.60; p < 0.0001), with a 52% reduction in risk of death or radiographic progression; benefit was observed across all subgroups analyzed. Median rPFS was not reached in the APA group and 22.1 mos in the PBO group. APA also significantly improved OS (HR, 0.67; 95% CI, 0.51-0.89; p = 0.0053), with a 33% reduction in risk of death. Median OS was not reached in the APA or PBO group. Time to initiation of cytotoxic chemotherapy was significantly improved with APA (HR, 0.39; 95% CI, 0.27-0.56; p < 0.0001). Based on these results, the independent data monitoring committee recommended unblinding to allow crossover of PBO pts to receive APA. Rates of grade 3/4 adverse events (AEs) (42% APA, 41% PBO) were similar, and discontinuations due to AEs (8% APA, 5% PBO) were low. Conclusions: In the TITAN study in pts with mCSPC, including pts with high- and low-volume disease and prior docetaxel, addition of APA to ADT significantly improved rPFS and OS, and the safety profile was tolerable. These results support the addition of APA to ADT for tx of pts with mCSPC. Clinical trial information: NCT02489318