Fred Saad, MD, University of Montreal Hospital Center, Quebec, Canada, discusses final results from the phase 3 ACIS trial, which compared radiographic progression-free survival of apalutamide vs placebo in combination with abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer (CRPC).

These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.

Transcript

Hello, my name is Fred Saad, I am professor and chairman of urology at the University of Montreal Hospital Centre. It is my pleasure to summarize data that was released at ASCO GU, the ACIS study.

This has been on for several years and randomized 982 patients between abiraterone prednisone and abiraterone prednisone plus apalutamide to try to determine whether combining two androgen receptor inhibitor agents together -- one that diminishes testosterone production and one that targets the androgen receptor -- would lead to better outcome than one agent alone.

The results showed that we were able to reach our primary end point, the primary end point being radiographic progression-free survival.

This was reduced by 31% of the risks of progression. This turned out to be about 6 months in the initial analysis, and with longer-term follow-up, turned out to be 7.4 months improvement in radiographic progression-free survival.

This is the first randomized trial with combination therapy that actually meets its primary end point. We are very happy with that, especially that historically, when we compared abiraterone to placebo in the initial 302 study, it was about an eight-month improvement in radiographic progression-free survival. We see that we improved that outcome significantly by adding apalutamide.

In terms of overall survival, secondary end point, this was improved by 2.5 months. Did not reach statistical significance in this study, but we did see other end points that were quite important, in terms of PSA declines, and especially PSA declines reaching to undetectable levels of below 0.2, which was statistically improved with the combination over abiraterone alone.

In terms of pre-planned subgroup analysis, we found that patients with visceral disease, either lung, liver, or adrenal, seemed to have even more benefit, in terms of radiographic progression-free survival and overall survival.

In the subgroup of patients over 75 years old, this improvement in overall survival turned out to be statistically significant by reducing the risk of death by 25%.

Quite interesting that both radiographic progression-free survival was improved and also in some of the subgroups, we tended to see improvements in overall survival.

It was reassuring that the addition of apalutamide to abiraterone and prednisone did not reduce quality of life. This was maintained throughout the study. The diminished quality of life occurred with a progression of the disease in this study.

In terms of safety adverse events, there was nothing unexpected with either drug. In combination, adverse event profiles were very similar to either one alone.

Overall, we are very happy with the results of this study meeting its primary end point. We are looking to work on biomarkers to try to determine who would benefit most from a combined approach.

Overall, in patients that are elderly that might not have easy access to chemotherapy, this might also be something of interest. It was a pleasure to be able to summarize this trial to you. Hopefully, this was helpful. Thank you very much.

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.