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)

R 2:1

Key eligibility criteria

• M0 CRPC
• Rising PSA with testosterone ≤ 50 ng/dL
• Baseline PSA ≥ 2 ng/L
• PSA doubling time ≤ 10 mo

Stratification factors

• PSA doubling time (< 6 mo vs 6-10 mo)
• Baseline use of bone-targeted agent

(Y vs N)

Primary endpoint

• Metastasis-free survival

(MFS)*

Secondary endpoints

• Time to PSA

progression

• Time to use of new

antineoplastic therapy

• Overall survival
• Safety
• PSA response

ENZA 160 mg/day + ADT n = 933 PBO + ADT n = 468

Abbreviations: ADT, androgen deprivation therapy; ENZA, enzalutamide; PBO, placebo; R, randomization.

*MFS was defined as time from randomization to radiographic progression or death on study

NCT02003924

Results: Primary and Secondary Endpoints

Abbreviations: CI, confidence interval; HR, hazard ratio; NR, not reached.

Metastasis-free survival, % 100 90 80 70 60 50 40 30 20 10 3 6 9 12 15 18 21 24 27 30 33 36 39 42 mo 933 468 865 420 759 296 637 212 528 157 431 105 418 98 328 64 237 49 159 49 87 16 77 11 31 5 4 1

• No. at risk

ENZA + ADT PBO + ADT

HR, 0.29 (95% CI, 0.24-0.35) p < .0001

PSA progression, % 100 90 80 70 60 50 40 30 20 10 3 6 9 12 15 18 21 24 27 30 33 36 39 42 mo 933 468 879 427 771 138 635 56 500 25 401 13 386 13 288 5 203 4 137 3 76 71 24 2

• No. at risk

ENZA + ADT PBO + ADT

HR, 0.21 (95% CI, 0.17-0.26) P < .0001 HR, 0.07 (95% CI, 0.05-0.08) p < .0001

First use of new antineoplastic therapy, % 100 90 80 70 60 50 40 30 20 10 mo 933 468 829 406 729 299 625 221 526 166 418 107 313 72 213 46 121 21 49 9 7 1

• No. at risk

ENZA + ADT PBO + ADT 4 8 12 16 18 24 28 32 36 40 44

HR, 0.21 (95% CI, 0.17-0.26) p < .0001

Overall survival, % 100 90 80 70 60 50 40 30 20 10 mo 933 468 884 447 805 403 716 351 621 303 521 247 414 194 298 135 169 78 75 31 13 6

• No. at risk

ENZA + ADT PBO + ADT 4 8 12 16 18 24 28 32 36 40 44

HR, 0.80 (95% CI, 0.58-1.09) p = .1519 ENZA PBO Median 36.6 14.7 (95% CI) mo (33.1-NR) (16.2-19.7) ENZA PBO Median 37.2 3.9 (95% CI) mo (33.1-NR) (3.8-4.0) ENZA PBO Median 39.6 17.7 (95% CI) mo (37.7-NR) (16.2-19.7) ENZA PBO Median NR NR (95% CI) mo (NR-NR) (NR-NR)

Results: PSA Response

• A significantly greater proportion of patients had confirmed PSA responses with ENZA vs PBO

76.3 55.9 9.6 2.4 0.4 20 40 60 80 100

≥ 50% ≥ 90% To undetectable level

Patients, % Confirmed PSA responses†

p < .0001 p < .0001 p < .0001

ENZA + ADT (n = 887) PBO + ADT (n = 439)

*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.

ENZA + ADT (n = 888) PBO + ADT (n = 441) Best percent change in PSA*

150 50

• 50
• 100

Safety and Conclusions

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

Median reporting period for AEs was 18.0 months (ENZA) vs 11.1 months (PBO).

Safety

AEs collected up to 30 days after last dose ENZA + ADT (n = 930) PBO + ADT (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)

Abbreviation: AE, adverse event.