Overall survival with abiraterone acetate and prednisone in PEACE-1

(UroToday.com) In this presentation, Dr Karim Fizazi discussed the updated results of PEACE-1, a phase 3 randomized trial in men with metastatic castration-sensitive prostate cancer (mCSPC) de novo. This update focused on overall survival (OS) for men treated with or without abiraterone plus prednisone (APA).

The last decade has seen a rapid change in standards of care (SOC) for first-line treatment in men with mCSPC. The PEACE-1 trial used a 2×2 design to assess (separately and in combination) the impact of adding PAA and radiation therapy (RT) to SOC therapy in men with mCSPC.

The control arm in this study has evolved to reflect contemporary SOC. When the study began enrolling patients, the SOC for first-line mCSPC was ADT alone. With the publication of data from the STAMEDE, LATITUDE and CHAARTED studies, the SOC was updated to include ADT plus Docetaxel 75 mg / m2 every 3 weeks for 6 cycles. The two experimental treatments studied in this study were: 1) PAA until disease progression or intolerance (concomitant with docetaxel) and 2) RT of the prostate (74 Gy in 37 fractions after the end of docetaxel). The results of the AAP experimental arm are discussed here.

The PEACE-1 study randomized 1,173 patients with 355 each in the SOC (with or without RT) and SOC (with or without RT) plus AAP arm. The demographic and baseline characteristics were similar in these two arms. Notably, about two-thirds of the patients in each arm had high volume disease.

PEACE-1 was designed with two primary endpoints for AAP analysis: radiographic progression-free survival (rPFS) and overall survival (OS). Dr Fizazi began by evaluating the benefit of adding PAA in the cohort of patients treated with SOC ADT plus Docetaxel (with or without RT). With a median follow-up of 3.8 years, adding PAA to SOC resulted in a 50% improvement in rPFS with a median rPFS of 2.0 years in the SOC arm and 4.5 years in the SOC arm. the SOC plus AAP arm (HR 0.50, 95% CI 0.40-0.62; P <0.0001). The benefit of rPFS was greater in the high volume subgroups than in the low volume subgroups, but both populations benefited. In patients with high volume disease, adding PAA to SOC resulted in a 53% improvement in rPFS with a median rPFS of 1.6 years in the SOC arm and 4, 1 year in the SOC plus AAP arm (HR 0.47, 95% CI 0.36-0.60; p <0.0001). Addition of PAA to SOC in patients with low volume disease resulted in a 42% improvement in rPFS with a median rPFS of 2.7 years in the SOC arm compared to the SOC arm plus PAA (HR 0.58, 95% CI 0.39-0.87; P = 0.006).

Similar results were observed for OS. Starting with the overall study population (ADT SOC with or without docetaxel), the addition of APA resulted in an 18% improvement in OS with a median OS of 4.7 years in the SOC arm and 5.7 years in the SOC plus AAP arm (HR 0.82, 95% CI 0.69-0.98; P = 0.030). By limiting itself to the cohort of patients who received ADT plus docetaxel as SOC, the addition of PAA resulted in a 25% improvement in OS with a median OS of 4.4 years in the SOC arm compared to what has not yet been achieved in the SOC plus AAP arm (HR 0.75, 95% CI 0.59-0.95; P = 0.017). This effect was observed in all subgroups, including those with high volume disease (HR 0.72, 95% CI 0.55-0.95) and low volume disease (HR 0.83 , 95% CI 0.50 to 1.38); interaction p-value 0.64. Notably, OS data is immature for low volume patients due to a small number of events.

An important consideration is the therapies that the patients received after the study treatment progressed. In particular, 81% of patients in the ADT plus Docetaxel SOC arm subsequently received next-generation hormone therapy. This suggests that early intensification with the addition of AAP to SOC results in improvement in rPFS and OS compared to sequential therapy.

In the cohort of patients who received ADT plus Docetaxel as SOC, the addition of AAP was well tolerated. There was no difference in the rates of grade 3 to 5 neutropenia or febrile neutropenia. As expected, grade 3 to 5 liver function abnormalities (6% vs. 1%) and hypertension (22% vs. 13%) were higher in patients who received SOC plus AAP compared to SOC alone .

Dr Fizazi put the results of PEACE-1 into context with previous randomized phase 3 studies for first-line treatment in high volume de novo mCSPC. Median OS ranged from 33 to 35 months for ADT alone, 40 to 48 months for ADT plus docetaxel, and 50 to 56 months for ADT plus AAP. The median OS for PEACE-1 was an impressive 61 months.

Dr Fizazi summarized that adding PAA to ADT plus docetaxel significantly improved the 2.5-year median rPFS in men with de novo mCSPC. OS was also improved with a 25% reduction in the risk of death, even when 81% of men in the control group subsequently received at least one new generation androgen signaling inhibitor. This advantage translates into a median lifetime gain of more than 1.5 years for men with high-volume metastatic disease (3.5 to 5.1 years). ILI data for men with low volume disease is immature and updates will be forthcoming. Dr Fizazi concluded that he believed these data were changing practice and that ADT plus Docetaxel plus AAP should be offered (at least) to men with de novo high volume mCSPC.

Presented by: Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy and professor of oncology at Paris-Saclay University in Villejuif, France

Written by: Jacob Berchuck, MD, Genitourinary Medical Oncologist, Dana-Farber Cancer Institute (Twitter: @jberchuck) at European Society for Medical Oncology (ESMO) 2021 Annual Meeting 2021, Thursday September 16, 2021 – Tuesday 21 September 2021.