PEACE-2: No cPFS benefit seen with added cabazitaxel

Investigators reported that adding cabazitaxel (Jevtana) to androgen deprivation therapy (ADT) and radiotherapy did not result in improved clinical progression-free survival (cPFS) and was associated with increased toxicity in men with very high-risk localized prostate cancer in the phase 3 PEACE-2 trial (NCT01952223).¹

The data were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium by Karim Fizazi, MD, PhD, a medical oncologist and head of the department of cancer medicine at the Institute of Gustave Roussy, and professor of oncology at the University of Paris Sud in Villejuif, France.

Patients were eligible for inclusion in PEACE-2 if they had very high-risk localized prostate cancer with at least 2 risk factors: Gleason score of at least 8, T3-T4 disease, or prostate-specific antigen (PSA) level of at least 20 ng/mL. A total of 761 patients were randomly assigned into 1 of 4 arms:

• arm A: androgen deprivation therapy (ADT) for 3 years plus prostate radiotherapy

• arm B: ADT plus radiotherapy of the pelvis

• arm C: ADT plus 4 cycles of cabazitaxel plus prostate radiotherapy

• arm D: ADT plus 4 cycles of cabazitaxel plus radiotherapy of the pelvis.

The primary end point was cPFS. Secondary end points included PSA response at 3 months, biochemical PFS, metastases-free survival, prostate cancer-specific survival, overall survival (OS), acute and long-term tolerance, quality of life, and biomarkers (biopsy).

For ADT, patients received either an LHRH agonist or an LHRH antagonist. Radiotherapy consisted of 74 Gy-78 Gy with 2-Gy fractions, with mandatory intensity-modulated radiation therapy. Radiotherapy was initiated 3 months following the start of ADT. Pelvic radiotherapy consisted of 46 Gy-50 Gy. Cabazitaxel treatment consisted of 20 mg/m²-25 mg/m² once every 3 weeks for 4 cycles.

Patients were accrued from 2013 to 2021 in 4 European countries. The median follow-up was 7.3 years (95% CI, 7.1-7.5). Fizazi said the investigators found no interaction between cabazitaxel and pelvic radiotherapy.

Baseline patient characteristics included a median age of 67 for arms A-C and 66 for arm D. In both arms A and B, 88% of patients had T3-T4 disease; in arms C and D, the rates were 91% and 93%, respectively. In arms B and D, 75% of patients had a Gleason score of 8-10; in arms A and C, the rates were 77% and 82%, respectively. In arms A and D, median PSA level was 22 ng/mL; for arms B and C, the median PSA level was 23 ng/mL and 19 ng/mL, respectively.

Fizazi reported that there was “no detectable difference” in cPFS at 7 years in patients receiving cabazitaxel vs patients who did not receive cabazitaxel, with cPFS rates of 62.8% (95% CI, 57.2-68.) and 67.2% (95% CI, 61.7-72.2), respectively (HR: 1.09; 95% CI, 0.85-1.38; P = 0.51).

Median bPFS was 10.2 years in patients receiving cabazitaxel vs 9.2 years in patients not receiving cabazitaxel (HR: 0.99; 95% CI, 0.78-1.27; P = 0.96). The HR for metastases-free survival was 1.09 (95% CI, 0.84-1.43; P =0.51).

Fizazi reported that the 9-year prostate cancer-specific survival rate was 90% (95% CI, 86-94) in patients receiving cabazitaxel vs 89% (95% CI, 84-93) in patients not receiving cabazitaxel (HR: 0.86; 95% CI, 0.50-1.47; P =0.57).

Fizazi said the safety findings of the study were what he and his coauthors expected. There were 74 (20%) instances of grade 3-4 neutropenia in patients receiving cabazitaxel compared with 1 (0%) instance in patients not receiving cabazitaxel. In addition, 13 (4%) instances of grade 3-4 diarrhea were observed in patients receiving cabazitaxel compared with 0 instances in patients not receiving cabazitaxel.

“In conclusion, cabazitaxel does not improve outcomes in very high-risk localized prostate cancer…With about 1 out of 10 patients dying from prostate cancer during the first decade, we may challenge the current definition of ‘very high-risk’ localized prostate cancer in men without nodal disease involvement. And this may prove even more true when modern imaging using PSMA-PET, for example, does not show nodal or metastatic dissemination,” Fizazi said. He also noted that the investigators plan to report on pelvic radiotherapy data at a future medical meeting.

REFERENCE

1. Fizazi K, Carles J, Foulon S, et al. Androgen deprivation therapy and radiotherapy with or without cabazitaxel in very-high risk localized prostate cancer: Results of the PEACE-2 randomized phase III trial. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA307. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16932