Dr. Nguyen on FORMULA-509 trial in prostate cancer

In this video, Paul L. Nguyen, MD, Dana-Farber Cancer Institute, Harvard Medical School, discusses the FORMULA-509 trial, which evaluated post-operative salvage radiotherapy and 6 months of GnRH agonist with or without abiraterone acetate (Zytiga)/prednisone and apalutamide (Erleada) post-radical prostatectomy. Nguyen presented this data at the 2023 ASCO Genitourinary Cancers Symposium (Abstract 303).

Transcript

The FORMULA-509 trial was a randomized multicenter trial with 345 patients looking specifically at the population of patients with a rising PSA after radical prostatectomy who are going to get salvage radiation and 6 months of a GnRH agonist. The question with FORMULA-509 was could we improve outcomes by randomizing patients to 6 months of abiraterone acetate and apalutamide in addition to their regular 6-month GnRH agonist versus the more standard 6 months of bicalutamide with their GnRH agonist. The primary end point was progression-free survival (PFS) and the secondary end point was metastasis-free survival (MFS). And importantly, and this comes up later, we stratified the trial by PSA greater than 0.5 vs less than 0.5, and by pathologic node positive vs node negative.

For the main result, it was a little bit of a heartbreaker. So the main PFS primary analysis didn't quite meet statistical significance. The hazard ratio was 0.71 with a one-sided P value of 0.06. And for MFS, it was similar, meaning the hazard ratio was 0.57, and the one-sided P value was 0.05. So we just missed statistical significance on the overall trial. But I think, looking at the data, it would be hard to say that there's no signal there—that there’s absolutely nothing going on. I think it just came very close and missed. And remember, there's only 34 months of follow-up at this point. And so I think with further follow up, we may well see a difference.

But where it got really interesting was for those pre-planned, pre-stratified subgroup analyses. So, specifically for the patient population with a PSA greater than 0.5, we found a very significant benefit in both PFS and MFS. So, the PFS hazard ratio for those patients was 0.5 with a two-sided P value of 0.03. And even more interestingly, was an MFS benefit, because we know that MFS is our surrogate for overall survival. The MFS benefit among these patients with a PSA greater than 0.5 showed a hazard ratio of 0.32 with a two-sided P value of 0.02. And the absolute magnitude of the benefit was 18%. So there's an 18% reduction at just 3 years in MFS. That means the number needed to treat is barely more than 5 patients to prevent 1 metastasis at 3 years; so very powerful effect size.

Transcript was edited for clarity.