A supplemental New Drug Application has been submitted to the FDA that seeks to expand the indication of abiraterone acetate in combination with prednisone and ADT to include treatment of patients with high-risk metastatic hormone-naive prostate cancer (mHNPC) or newly diagnosed, high-risk metastatic hormone-sensitive prostate cancer (HSPC).
The filing is based on phase III data from the pivotal LATITUDE clinical trial, which found that in newly diagnosed patients with high-risk mHNPC, abiraterone acetate in combination with prednisone and ADT significantly increased overall survival (OS) and radiographic progression-free survival (rPFS), compared to placebo plus ADT.
LATITUDE was a multinational, multicenter, randomized, double-blind, placebo-controlled clinical trial that examined the use of abiraterone acetate 1,000 mg once daily in combination with prednisone 5 mg once daily and ADT, compared to placebo plus ADT (N=1,199) in patients with newly diagnosed, high-risk mHNPC (NEJM 2017; 377:352-360).
The LATITUDE study showed abiraterone acetate in combination with prednisone and ADT reduced the risk of death by 38 percent compared to placebo plus ADT (median OS not reached vs. 34.7 months, respectively; hazard ratio: 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001) in patients with mHNPC. Additional study results found patients with mHSPC who received abiraterone acetate in combination with prednisone and ADT had a 53 percent lower risk of radiographic progression or death, compared to placebo plus ADT (median rPFS 33.0 months vs. 14.8 months, respectively, HR: 0.47; 95% CI, 0.39 to 0.55; P<0.001). Concerning the secondary endpoints, abiraterone acetate in combination with prednisone and ADT reduced the risk of pain progression by 31 percent (HR=0.695; 95% CI: 0.583, 0.829; P<0.0001) and skeletal-related events by 30 percent (HR=0.703; 95% CI: 0.539, 0.916; p=0.0086), as well as reduced the risk of needing to start chemotherapy by 56 percent (HR=0.443; 95% CI: 0.349, 0.561, P<0.0001) compared to placebo plus ADT.
Additional data, presented at the ESMO 2017 Congress, demonstrated clinically meaningful and statistically significant improvements in patient-reported outcomes. Abiraterone acetate in combination with prednisone and ADT significantly delayed the time to health-related quality of life degradation by 15 percent (HR=0.853; 0.736, 0.989; p=0.0322) and significantly delayed the time to worst fatigue intensity progression by 35 percent (HR=0.652; 95% CI: 0.527, 0.805; P=0.0001) for patients with mHNPC.
Overall, the safety profile of abiraterone acetate in combination with prednisone and ADT, was similar to prior studies in patients with metastatic castration-resistant prostate cancer. Grade 3/4 events reported in >=5 percent of patients were hypertension (20%/0% vs. 10%/0.2%), hypokalemia (10%/0.8% vs. 1%/0.2%), and increase in alanine aminotransferase (5%/0.3% vs. 1%/0%) in abiraterone acetate in combination with prednisone and ADT versus placebo plus ADT groups, respectively.