Adding apalutamide to abiraterone and prednisone improved radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to a study published in The Lancet Oncology.

The phase 3 ACIS study (ClinicalTrials.gov Identifier: NCT02257736) included 982 men with mCRPC from 167 hospitals in 17 countries.

The patients were randomly assigned to receive apalutamide plus abiraterone acetate and prednisone (492 patients) or placebo plus abiraterone-prednisone (490 patients).


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At a median follow-up of 25.7 months, the median rPFS was 22.6 months for the apalutamide arm and 16.6 months for the placebo arm (hazard ratio [HR], 0.69; 95% CI, 0.58-0.83; P <.0001).

At an updated analysis with a median follow-up of 54.8 months, the median rPFS was 24.0 months in the apalutamide arm and 16.6 months in the placebo arm (HR, 0.70; 95% CI, 0.60-0.83; P <.0001).

The proportion of patients who reached undetectable prostate-specific antigen (PSA) concentrations at any time during treatment was significantly higher in the apalutamide arm than in the placebo arm — 25% and 19%, respectively (HR, 1.28; 95% CI, 1.01-1.62; P =.040).

On the other hand, there were no significant differences in median time to PSA progression, overall response rate, or overall survival.

The median overall survival was 36.2 months in the apalutamide arm and 33.7 months in the placebo arm (HR, 0.95; 95% CI, 0.81-1.11; P =.50). The median time to PSA progression was 13.8 months and 12.0 months, respectively (HR, 0.87; 95% CI, 0.74-1.02; P =.076). The overall response rate was 58% and 53%, respectively (HR, 1.10; 95% CI, 0.91-1.33; P =.33).

The most common grade 3/4 treatment-emergent adverse event was hypertension, which occurred in 17% of patients in the apalutamide arm and 10% of patients in the placebo arm.

Fatal treatment-related adverse events (TRAEs) occurred in 3 patients in the apalutamide arm — 2 cases of pulmonary embolism and 1 cardiac failure.

Fatal TRAEs occurred in 5 patients in the placebo arm — 1 cardiac failure, 1 cardiac arrest, 1 mesenteric arterial occlusion, 1 seizure, and 1 sudden death.

“The ACIS study highlighted potential long-term clinical benefits associated with the combination of apalutamide and abiraterone-prednisone in clinical subgroups of patients,” the researchers wrote. “However, these results require further exploration.”

Disclosures: This research was supported by Janssen Research & Development. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Saad F, Efstathiou E, Attard G, et al. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): A randomized, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. Published online September 30, 2021. doi:10.1016/S1470-2045(21)00402-2