Apalutamide added to abiraterone acetate plus prednisone improves radiographic progression-free survival (rPFS) by 7.4 months vs abiraterone acetate plus prednisone alone in metastatic castration-resistant prostate cancer, according to results from a final analysis of the ACIS trial presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.

“Metastatic castration-resistant prostate cancer is frequently driven by activated androgen receptors and elevated intratumoral antigens. Apalutamide, an androgen receptor inhibitor, and separately, abiraterone acetate plus prednisone, which suppresses the antigen ligand, are approved prostate cancer therapies,” explained Dana E Rathkopf, MD, Memorial Sloan Kettering Cancer Center, New York, during her presentation.

The phase 3 ACIS trial aimed to assess rPFS with abiraterone acetate plus prednisone with or without apalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer. The primary end point was rPFS. Overall survival (OS) was a secondary end point.

A total of 982 patients were enrolled in the trial and randomized in a 1:1 ratio to receive apalutamide or placebo plus abiraterone acetate plus prednisone.

In the primary analysis, after a median follow-up of 25.7 months, apalutamide and abiraterone acetate plus prednisone extended median rPFS by 6 months with a 31% reduction in the risk of radiographic progression or death vs abiraterone acetate plus prednisone alone (22.6 months vs 16.6 months; hazard ratio [HR] 0.69).

At the updated final analysis, after a median follow-up of 54.8 months, apalutamide and abiraterone acetate plus prednisone extended median rPFS by 7.4 months with a 30% reduction in the risk of radiographic progression or death (24 months vs 16.6 months; HR 0.70).

In addition, at 54.8 months follow-up, median OS was improved with apalutamide and abiraterone acetate plus prednisone (36.2 months vs 33.7 months), though not statistically significant.

"In conclusion, ACIS met its primary endpoint. Radiographic PFS, as assessed by investigative review, was extended by 6 months in the primary per protocol analysis, and by 7.4 months in the updated final analysis with apalutamide plus abiraterone vs the active comparator, abiraterone alone,” concluded Dr Rathkopf.—Janelle Bradley

Rathkopf DE, Efstathiou E, Attard G. Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC). Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 9.