Escalated ADT is insufficient in men with high-risk features after prostatectomy

SAN FRANCISCO — Adding hormone therapy plus antiandrogens to salvage radiation and androgen deprivation therapy (ADT) did not improve survival outcomes in high-risk prostate cancer.

Addition of 6 months of abiraterone acetate (Zytiga) and apalutamide (Erleada) to salvage radiation therapy (RT) and 6 months of ADT in the FORMULA-509 trial and GnRH agonists failed to statistically significantly improve survival (PFS) and metastasis-free survival (MFS) after progression-free radical prostatectomy in men with high-risk features and detectable PSA.

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

Nguyen also noted that “6 months of intensive [AD T] use of next-generation anti-androgenic Hormonal agents may be an attractive alternative to prolonging ADT.”

FORMULA-509 randomized 305 patients with PSA ≥ 0.1 – radical prostatectomy and one or more Unfavorable risk factors, receiving salvage radiotherapy plus 6 months of GnRH agonist versus standard first-generation antiandrogen bicalutamide (Casodex) or next-generation antiandrogen abiraterone acetate/prednisone (AAP) and apalutamide (Apa).

The median age of the patients was 65 years, 35% had a Gleason score of 9, the median PSA was 0.03, and 31% had a PSA>0.5, 29% were pathological nodes, “so this is a pretty high-risk population,” observed Nguyen. The annual PFS was 74.9% compared with 68.5% for bicalutamide (hazard ratio 0.71, 95% CI 0.49-1.03, P=0.06). The 3-year MFS rates were 90.6% and 87.2%, respectively (HR 0.57, 90% CI 0.33-1.01, P=0.05).

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

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

According to Nguyen and colleagues, no statistically significant benefit of AAP/Apa was detected in preplanned analyzes in stratified subgroups defined by PSA ≤ 0.5 or pathological node-negative or node-positive status.

Nguyen concedes that “we shouldn’t compare clinical trials,” but says FORMULA-509’s results on MFS appear to be better than those of the RADICALS-HD trial, which evaluated 24 months ADT compared with a control arm of 6-month ADT in the rescue patient population.

“Of course, this has to be formally tested…but what will FORMULA-509 do at 24 months of ADT?” he said. “And I think, compared to 6-month ADT, we can say it’s definitely doing well on the court. So, for patients with higher-risk characteristics, I think stepping up to 6-month ADT might be an option for extending ADT. An attractive alternative has a duration of 24 months.” He said this approach will be tested in the PROSTATE IQ study.

GuCS discussant Tyler Seibert, MD, University of California, San Diego, stated that the “strongest evidence”24 The follow-up of several months of ADT treatment has been well established.

However, he noted that “6 months of intensification is very compelling,” emphasizing that patients with PSA>0.5 did benefit from 6 months of AAP/Apa, “and No small benefit.”

Seibert said it would be interesting to see how patients responded when a full comparison was made, evaluating a multidrug regimen for 6 months versus a GnRH agonist alone for 24 months. moon. “We may see that, even with similar outcomes, many patients would prefer 6 months of more intense treatment to 2 years of androgen deprivation therapy with all the quality of life compromises,” he said.