LBA5_PR - A phase III trial with a 2x2 factorial design in men with de novo metastatic castration-sensitive prostate cancer: Overall survival with abiraterone acetate plus prednisone in PEACE-1

Background

Since 2015, combining androgen deprivation therapy (ADT) with either docetaxel, androgen signaling inhibitors (ASI), or radiotherapy to the primary tumor (RXT) (for low metastatic burden) was shown to improve overall survival (OS) and has thus become the new standard of care (SOC) in men with mCSPC. It is unknown whether combining those treatments on top of ADT could further increment outcomes. PEACE-1 is a phase 3 trial with a 2x2 factorial design of abiraterone acetate plus prednisone (abiraterone) and/or local radiotherapy. First results show that adding abiraterone to ADT+docetaxel significantly improves rPFS in men with mCSPC (HR: 0.50 (0.40-0.62), p<0.0001) (Fizazi, ASCO 2021).

Methods

1173 men (57% high-, 43% low-volume) with de novo mCSPC were randomized to SOC, SOC+abiraterone, SOC+RXT or SOC+abiraterone+RXT (SOC was ADT+docetaxel for 710 pts). The overall type I error testing the abiraterone effect was 5% (4.9% for OS, 0.1% for rPFS). In the ADT+docetaxel population, 249 events were required to detect an HR of 0.70 for OS with 80% power.

Results

The median follow-up is 4.4 yrs (n=273 death events in the ADT+docetaxel population). The effect of abiraterone on OS did not interact with the one of RXT (p=0.82) allowing to pool the abiraterone arms together for comparison. OS was improved by abiraterone both in the overall population (HR: 0.83, 95% CI: 0.69-0.99, p=0.034; medians: 5.7 vs 4.7 yrs) and in the ADT+docetaxel population (HR: 0.75, 95% CI: 0.59-0.96, p=0.021; medians: NR vs 4.4 yrs). Among the ADT+docetaxel pts who developed CRPC, 231/263 (88%) then received at least one life-prolonging therapy and 222/263 (84%) at least one ASI in the control arm, compared to 110/141 (78%) and 67/141 (48%) in the abiraterone arm, respectively. Grade 3-5 adverse events reported in >5% of pts in the ADT+docetaxel population included neutropenic fever (5% vs 5%), neutropenia (10% vs 9%), liver toxicity (6% vs 1%) and hypertension (21% vs 13%) in the abiraterone and control arms, respectively.

Conclusions

Adding abiraterone to ADT plus docetaxel improves both rPFS and OS in mCSPC men, even when 84% of mCRPC men from the control arm receive an ASI.

Clinical trial identification

NCT01957436.

Editorial acknowledgement

We thank Sébastien Marion from Unicancer for editing the English.

Legal entity responsible for the study

Unicancer.

Funding

Janssen Pharmaceutical NV, Ipsen, Sanofi, PHRC.

Disclosure

K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Curevac; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer; Financial Interests, Institutional, Research Grant, Trial chair: Bayer; Financial Interests, Institutional, Research Grant, Trial chair: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Orion; Financial Interests, Institutional, Research Grant, Trial chair: MSD; Financial Interests, Institutional, Research Grant, Trial chair: BMS; Financial Interests, Institutional, Research Grant, Trial chair: Janssen. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Janssen. G. Roubaud: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Pfizer. R. McDermott: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Clovis; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Regeneron. A. Fléchon: Financial Interests, Personal, Expert Testimony: AAA; Financial Interests, Personal, Expert Testimony: Astrazeneca; Financial Interests, Personal, Expert Testimony: Astellas; Financial Interests, Personal, Expert Testimony: Bayer; Financial Interests, Personal, Expert Testimony: Janssen; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Sanofi. B. Tombal: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Ferring; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Advisory Board: Sanofi. S. Supiot: Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bouchara; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Principal Investigator: Astrazeneca; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Janssen. D.R. Berthold: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche. G. Kacso: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: MSD. G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Sanofi. F. Calabro': Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Astrazeneca; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Pfizer. A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Astrazeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Astellas. I. Latorzeff: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen. A. Bossi: Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Bard; Financial Interests, Personal, Advisory Role: Elekta; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Ferring; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Invited Speaker: Janssen. All other authors have declared no conflicts of interest.