Evolving Treatment Landscape for Metastatic Hormone-Sensitive Prostate Cancer

In a presentation at the 2022 Great Debates and Updates in Genitourinary Oncology meeting, Oliver Sartor, MD, Tulane Cancer Center, New Orleans, LA, discussed the evolving treatment landscape for metastatic hormone-sensitive prostate cancer.

Dr Sartor focused on 3 trials to summarize recent updates: PEACE-1, ARASENS, and STAMPEDE.

The PEACE-1 trial included patients with de novo metastatic castration-sensitive prostate cancer with distant lesions detected on bone scan or CT scan. All patients were receiving androgen deprivation therapy (ADT).

Patients were randomized in a 1:1:1:1 ratio to receive ADT plus docetaxel, ADT plus docetaxel and abiraterone, ADT plus docetaxel and radiotherapy, or ADT plus docetaxel and abiraterone with radiotherapy.

The addition of radiotherapy resulted in no difference, so the study consolidated into 2 groups: ADT plus docetaxel vs ADT and docetaxel plus abiraterone. The median radiographic progression-free survival (PFS) was 2 months for ADT plus docetaxel vs 4.5 months with the addition of abiraterone (hazard ratio [HR] 0.5, P <.0001). The median overall survival (OS) was 4.4 years vs not reached (HR 0.75, P = .017), respectively.

Dr Sartor segued into long-term follow-up data from the STAMPEDE trial, which evaluated ADT plus abiraterone and prednisone for hormone-naïve metastatic prostate cancer. Patients were randomized in a 1:1 ratio to ADT alone vs ADT plus abiraterone and prednisone. The median OS was 3.8 years vs 6.6 years, respectively.

“We certainly see that the addition of abiraterone, even without the use of docetaxel, is clearly a very positive event,” said Dr Sartor.

In a comparison of high-volume subsets from various trials presented at the 2021 ESMO Meeting, the median OS with PEACE-1 was 61 months vs 56 months with STAMPEDE. “I think a lot of people are probably going to use the triplets in the young fit person with a high-volume disease,” said Dr Sartor.

The ARASENS trial is an international, phase 3 trial that randomized patients in a 1:1 ratio to receive darolutamide or placebo in combination with ADT and docetaxel. In this trial, ADT plus docetaxel and darolutamide resulted in a 32.5% reduction in the risk of death (HR 0.68, 95% CI 0.57–0.80; P <.001) compared with placebo.

The most recent STAMPEDE data looked at ADT vs ADT plus abiraterone and prednisone with or without enzalutamide in patients who had at least 2 of the following: tumor stage T3 or T4, Gleason score of 8–10, and prostate-specific antigen concentration ≥40 ng/mL, or were relapsed with high-risk features.

Researchers found that the addition of enzalutamide made no difference, so this data was combined, and the study was consolidated into 2 subsets. For ADT plus abiraterone and prednisone with or without enzalutamide, the metastasis-free survival HR was 0.53 and OS HR was 0.6. When looking at prostate cancer specific survival, this HR dropped down to 0.49.

Looking at what’s next, Dr Sartor highlighted a few studies to look out for: PSMAddition comparing 177Lu-PSMA-617 in combination with standard of care vs standard of care alone, CAPItello-281 looking at capivasertib plus abiraterone, TALAPRO-3 looking at talazoparib with enzalutamide, and STAMPEDE now looking at metformin and the role of transdermal estrogen in replace of ADT.

Source:
Sartor O. Evolving Landscape of Treatment for mHSPC. Presented at: 2022 Great Debates and Updates in Genitourinary Oncology; March 9-11, 2022; virtual. Accessed March 30, 2022.