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SAN FRANCISCO -- Add-on hormone therapy plus an antiandrogen to salvage radiation and androgen deprivation therapy (ADT) did not boost survival outcomes in high-risk prostate cancer.

In the trial, the addition of 6 months of abiraterone acetate (Zytiga) and apalutamide (Erleada) to salvage radiation (RT) and 6 months of ADT with a GnRH agonist failed to statistically significantly improve progression-free survival (PFS) and metastasis-free survival (MFS) in men with high-risk features and detectable PSA after radical prostatectomy, reported Paul Nguyen, MD, MBA, of the Dana-Farber Cancer Institute and Brigham and Women's Hospital, both in Boston.

However, the primary analysis "strongly suggested that the trial's treatment regimen may improve PFS in patients with a PSA >0.5 after radical prostatectomy, he said in a presentation at the ASCO Genitourinary Cancers Symposium (GuCS).

Nguyen also noted that "6 months of intensified [ADT] with next-generation antiandrogens may be an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features following radical prostatectomy."

FORMULA-509 randomized 305 patients with PSA ≥0.1 post-radical prostatectomy, and one or more unfavorable risk factors, to receive salvage RT plus 6 months of a GnRH agonist with either the standard first-generation antiandrogen bicalutamide (Casodex) or next-generation antiandrogens abiraterone acetate/prednisone (AAP) and apalutamide (Apa).

The median age of patients was 65, 35% had Gleason score of 9, the median PSA was 0.03 with 31% having a PSA >0.5, and 29% were pathologic node positive,"so this was a pretty high-risk population," Nguyen observed.

He reported that at a follow-up of 34 months, those patients who received AAP/Apa had a 3-year PFS of 74.9% versus 68.5% with bicalutamide (hazard ratio 0.71, 95% CI 0.49-1.03, P=0.06). The 3-year MFS rate was 90.6 versus 87.2%, respectively (HR 0.57, 90% CI 0.33-1.01, P=0.05).

The study was powered to detect a HR of 0.50 for PFS and a HR of 0.30 for MFS, each with 80% power and one-sided type I error of 0.05, and thus failed to achieve a statistically significant benefit with AAP/Apa for both endpoints.

However, in a prespecified, preplanned subgroup analysis of men with a PSA >0.05, the investigators reported a 3-year PFS of 67.2% and 46.8% in the with AAP/Apa and bicalutamide groups, respectively (HR 0.50 95% CI 0.27-0.95, P=0.03). The 3-year MFS was 84.3% versus 66.1%, respectively (HR 0.32, 95% CI 0.13-0.84, P=0.02).

No statistically significant benefit was detected with AAP/Apa in pre-planned analyses of stratification subgroups defined by PSA ≤0.5, or pathological node-negative or node-positive status, according to Nguyen and colleagues.

Nguyen acknowledged that "we're not supposed to compare clinical trials," but said the results of FORMULA-509 regarding MFS seemed to compare favorably with those of the trial, which evaluated 24 months of ADT against a control arm of 6 months of ADT in a salvage patient population.

"Of course, this has to be formally tested...but is FORMULA-509 performing in the ballpark of what 24 months of ADT would do?" he said. "And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark. So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months." He said this approach will be tested in the PROSTATE IQ study.

GuCS discussant Tyler Seibert, MD, PhD, of the University of California San Diego, said that the "" for 24 months of ADT therapy was well established in the RADICALS-HD trial, considering it's size (>1,500 patients), and 10-year follow-up.

But he noted that "intensification for 6 months is very compelling" and emphasized that the PSA >0.5 patients did benefit from 6 months of AAP/Apa, "and not in in a small way."

Seibert said it will be interesting to see how patients react once a full comparison is available, assessing 6 months with the multiple-medication regimen versus 24 months with a GnRH agonist alone. "We may see that, even if the results are similar, that many patients would rather have 6 months of more intense therapy than do 2 years of androgen deprivation with all of the quality-of-life implications," he stated.

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