Prostate-specific antigen (PSA) response in men with nonmetastatic - PowerPoint PPT Presentation

Prostate-specific antigen (PSA) response in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC) treated with enzalutamide: results from PROSPER Cora N. Sternberg, Karim Fizazi, Fred Saad, Per Rathenborg, Neal Shore, Eren Demirhan, Katharina Modelska, De Phung, Andrew Krivoshik, and Maha Hussain

Prostate-specific antigen (PSA) response in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC) treated with enzalutamide: results from PROSPER Conflict of Interest Disclosure I have the following potential conflict(s) of interest to report: • Honoraria or institutional research funding from Pfizer, Astellas, Sanofi, Janssen, Bayer, Clovis Oncology, and Ferring

PROSPER Study Design (N = 1401) Primary endpoint Key eligibility criteria • Metastasis-free survival ENZA • M0 CRPC (MFS)* 160 mg/day + • Rising PSA with testosterone ≤ 50 ng/dL ADT Secondary endpoints • Baseline PSA ≥ 2 ng/L n = 933 R • Time to PSA • PSA doubling time ≤ 10 mo 2:1 progression PBO + • Time to use of new Stratification factors ADT antineoplastic therapy • PSA doubling time (< 6 mo vs 6-10 mo) n = 468 • Overall survival • Baseline use of bone-targeted agent • Safety (Y vs N) • PSA response *MFS was defined as time from randomization to radiographic progression or death on study NCT02003924 Abbreviations: ADT, androgen deprivation therapy; ENZA, enzalutamide; PBO, placebo; R, randomization.

Results: Primary and Secondary Endpoints HR, 0.07 (95% CI, 0.05-0.08) 100 HR, 0.29 (95% CI, 0.24-0.35) 100 90 90 p < .0001 p < .0001 Metastasis-free survival, % 80 80 PSA progression, % 70 70 60 60 50 50 ENZA PBO 40 40 Median 37.2 3.9 30 ENZA PBO 30 HR, 0.21 (95% CI, 0.17-0.26) 20 (95% CI) mo (33.1-NR) (3.8-4.0) Median 36.6 14.7 20 P < .0001 10 10 (95% CI) mo (33.1-NR) (16.2-19.7) 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 mo mo No. at risk No. at risk ENZA + ADT 933 865 759 637 528 431 418 328 237 159 87 77 31 4 0 ENZA + ADT 933 879 771 635 500 401 386 288 203 137 76 71 24 2 0 PBO + ADT 468 420 296 212 157 105 98 64 49 49 16 11 5 1 0 PBO + ADT 468 427 138 56 25 13 13 5 4 3 0 0 0 0 0 HR, 0.21 (95% CI, 0.17-0.26) 100 100 First use of new antineoplastic p < .0001 90 90 80 80 Overall survival, % 70 70 therapy, % 60 60 ENZA PBO 50 50 Median NR NR 40 40 (95% CI) mo (NR-NR) (NR-NR) ENZA PBO 30 30 20 Median 39.6 17.7 20 HR, 0.80 (95% CI, 0.58-1.09) 10 10 p = .1519 (95% CI) mo (37.7-NR) (16.2-19.7) 0 0 0 4 8 12 16 18 24 28 32 36 40 44 0 4 8 12 16 18 24 28 32 36 40 44 mo mo No. at risk No. at risk ENZA + ADT ENZA + ADT 933 829 729 625 526 418 313 213 121 49 7 0 933 884 805 716 621 521 414 298 169 75 13 0 PBO + ADT PBO + ADT 468 406 299 221 166 107 72 46 21 9 1 0 468 447 403 351 303 247 194 135 78 31 6 0 Abbreviations: CI, confidence interval; HR, hazard ratio; NR, not reached.

Results: PSA Response ENZA + ADT (n = 887) 150 PBO + ADT (n = 439) 100 p < .0001 Best percent change in PSA* 76.3 p < .0001 80 Patients, % 50 55.9 60 40 p < .0001 20 -50 9.6 2.4 0.4 0 0 -100 ≥ 50% ≥ 90% To undetectable level ENZA + ADT (n = 888) PBO + ADT (n = 441) Confirmed PSA responses † • A significantly greater proportion of patients had confirmed PSA responses with ENZA vs PBO * Includes patients with ≥ 1 postbaseline PSA assessment. † Includes patients with ≥ 2 consecutive PSA assessments ≥ 3 weeks apart. p value was based on stratified Cochran-Mantel-Haenszel mean score test.

Safety and Conclusions Safety ENZA + ADT PBO + ADT AEs collected up to 30 days after last dose (n = 930) (n = 465) Any AE, no. (%) 808 (86.9) 360 (77.4) Any grade ≥ 3 AE 292 (31.4) 109 (23.4) AE as primary reason for discontinuation 87 (9.4) 28 (6.0) Grade 5 AEs 32 (3.4) 3 (0.6) Median reporting period for AEs was 18.0 months (ENZA) vs 11.1 months (PBO). Conclusions • In M0 CRPC, 71% relative risk reduction of metastasis or death with ENZA vs PBO • PSA responses significantly greater with ENZA vs PBO • Time to first use of new antineoplastic therapy and time to PSA progression significantly longer with ENZA vs PBO; positive trend for overall survival • ENZA well tolerated; AEs consistent with established safety profile Abbreviation: AE, adverse event.