Abiraterone Shows Durable Survival Benefit in De Novo Metastatic CSPC

At the 2026 European Society for Medical Oncology (ESMO) Congress, Karim Fizazi, MD, PhD, a medical oncologist at Institut Gustave Roussy and Centre Oscar Lambret, presented a preplanned long-term analysis of the phase 3 PEACE-1 trial (NCT01957436) in patients with de novo metastatic castration-sensitive prostate cancer (CSPC). After a median follow-up of 7.7 years, adding abiraterone acetate (Zytiga) plus prednisone to standard of care continued to improve overall survival (OS), with benefit including patients who received triplet therapy with androgen deprivation therapy (ADT) and docetaxel.¹

Docetaxel and androgen receptor pathway inhibitors (ARPIs) have each improved OS in metastatic CSPC, but most pharmaceutical-sponsored trials follow patients for 5 years or less. Long-term data on triplet therapy have been limited. The primary PEACE-1 analysis in 2021 published in The Lancet, at a median follow-up of 3.5 years, showed that abiraterone improved OS and that triplet therapy outperformed doublet therapy.²

In the overall population of 1172 patients, the median OS was 6.1 years (95.1% CI, 5.3-6.6) with abiraterone vs 4.6 years (95.1% CI, 4.2-5.2) without it (adjusted HR, 0.75; 95.1% CI, 0.65-0.87; P = .0001). The 7-year OS rates were 44.9% (95.1% CI, 40.8%-49.2%) vs 34.2% (95.1% CI, 30.3%-38.3%), and the 8-year rates were 40.3% (95.1% CI, 36.0%-44.8%) vs 29.5% (95.1% CI, 25.6%-33.8%). The median radiographic progression-free survival (rPFS) was 4.3 years (95% CI, 3.2-5.5) with abiraterone vs 2.2 years (95% CI, 1.8-2.6) without it (HR, 0.55; 95% CI, 0.44-0.70; P <.0001).

The benefit held among the 710 patients who received ADT plus docetaxel. In this group, the median OS was 6.2 years (95.1% CI, 5.2-7.3) with triplet therapy vs 4.4 years (95.1% CI, 4.0-4.9) with doublet therapy (adjusted HR, 0.68; 95.1% CI, 0.56-0.82; P <.0001). The 7-year OS rates were 45.7% (95.1% CI, 40.3%-51.2%) vs 30.7% (95.1% CI, 25.8%-36.1%). The median rPFS was 4.1 years (99.9% CI, 3.0-5.9) vs 2.0 years (99.9% CI, 1.6-2.5; adjusted HR, 0.50; 99.9% CI, 0.38-0.68; P <.0001), and the 7-year rPFS rates were 37.0% (99.9% CI, 28.8%-46.1%) vs 14.5% (99.9% CI, 9.2%-22.2%).

Patients with high-volume metastatic disease had a median OS of 4.6 years (95.1% CI, 3.9-6.1) with triplet therapy vs 3.5 years (95.1% CI, 3.2-4.0) with doublet therapy (adjusted HR, 0.67; 95.1% CI, 0.54-0.85; P = .0007). Their 7-year OS rates were 40.9% (95.1% CI, 34.4%-47.7%) vs 22.4% (95.1% CI, 17.2%-28.7%), nearly doubling the proportion of long-term survivors. Patients with low-volume disease had a median OS of 7.8 years (95.1% CI, 6.4-not estimable) vs 6.2 years (95.1% CI, 5.4-8.1; adjusted HR, 0.74; 95.1% CI, 0.51-1.05; P = .091), and the 7-year OS rates were 54.2% (95.1% CI, 45.0%-63.1%) vs 46.0% (95.1% CI, 36.9%-55.4%). The interaction test between treatment effect and disease volume was not significant (P = .5552).

The benefit of abiraterone persisted even though 86% of patients in the control arm received an ARPI after progression.

PEACE-1 used a 2 × 2 factorial design. From November 2013 to December 2018, patients with de novo metastatic CSPC and an ECOG performance status of 0 to 2 were randomly assigned 1:1:1:1 to one of 4 arms:

• standard of care (n = 296);
• standard of care plus abiraterone (n = 292);
• standard of care plus radiotherapy (n = 293);
• standard of care plus abiraterone and radiotherapy (n = 292).

All patients received continuous ADT. A protocol amendment allowed docetaxel once it had been shown to improve OS. Randomization was stratified by ECOG performance status, metastatic sites, type of castration and docetaxel use. The trial found no interaction between the effects of abiraterone and those of radiotherapy, and in the primary analysis, radiotherapy did not improve OS.

Baseline characteristics were balanced between patients who did and did not receive abiraterone. The median age was 66 years (IQR, 59-72) vs 67 years (IQR, 61-72) in the control and abiraterone arms, respectively, about 75% of patients had a Gleason score of 8 or higher, and 57% had high-volume disease.

No new long-term safety signals emerged. In the ADT plus docetaxel population, the most notable grade 3 or 4 adverse events with triplet vs doublet therapy were:

• hypertension (21% vs 14%);
• hypokalemia (4% vs 1%);
• neutropenia (10% vs 12%);
• febrile neutropenia (5% vs 6%).

Fizazi concluded that abiraterone clearly improves long-term survival in de novo metastatic CSPC and that triplet therapy is active regardless of metastatic volume. He added that early treatment is better than treatment at progression, given that nearly all patients in the control arm received an ARPI after progression.

Disclosures

Fizazi reported receiving honoraria paid to his institution from Bayer, Johnson & Johnson, Merck/MSD, Novartis/AAA, and Servier; scientific advisory board participation, with payments to his institution, for AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Merck/MSD, Novartis/AAA, Pfizer, and Vir Oncology; and travel and accommodation support from AstraZeneca, Bayer, Johnson & Johnson, Merck/MSD, Novartis/AAA, Pfizer, and Servier.

References

1. Fizazi K, Foulon S, Carles J, et al. Long-term overall survival with abiraterone acetate plus prednisone in the PEACE-1 phase 3 trial for de novo metastatic castration-sensitive prostate cancer (mCSPC). Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 2215O.
2. Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022;399(10336):1695-1707. doi:10.1016/S0140-6736(22)00367-1