Cabazitaxel Plus ADT/Radiotherapy Fails to Show Long-Term Survival Benefit in High-Risk Localized Prostate Cancer

The addition of cabazitaxel to long-term androgen deprivation therapy (ADT) and radiotherapy failed to significantly improve progression-free survival (PFS), metastasis-free survival (MFS), or overall survival (OS), and resulted in a greater incidence of higher-grade toxicities compared with ADT and radiotherapy alone in patients with high-risk localized prostate cancer, according to final results from the PEACE-2 trial (NCT01952223) presented at the 2026 Genitourinary Cancers Symposium.¹

At a median follow-up of 7.3 years (95% CI, 7.1-7.5), the clinical PFS (cPFS) rate was 62.8% (95% CI, 57.2%-68.0%) with the cabazitaxel regimen vs 67.2% (95% CI, 61.7%-72.2%) with the standard of care (SOC) regimen (adjusted HR, 1.09; 95% CI, 0.85-1.38; P = .51). Furthermore, the median biochemical PFS (bPFS) was 10.2 years vs 9.2 years with the cabazitaxel vs standard regimen (adjusted HR, 0.99; 95% CI, 0.78-1.27; P = .96). No significant differences in MFS and OS were observed between the 2 arms (adjusted HR, 1.09; 95% CI, 0.84-1.43; P = .51). However, both groups achieved a prostate cancer–specific survival (PCSS) rate of approximately 90% at 9 years (HR, 0.86; 95% CI, 0.50-1.47; P = .57).

Presenting author Karim Fizazi, MD, PhD, and colleagues asserted that this relatively high PCSS rate not only indicates that high-risk patients do better than expected on ADT plus radiotherapy alone, but may indicate the need for a new conceptualization of “very high-risk” disease.

“With [this study showing approximately] 1 in 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,” Fizazi stated during his oral presentation of the data. “This may prove even more true when modern imaging, for example PSMA/PET, does not show nodal or metastatic dissemination.”

Fizazi is a medical oncologist at Institut Gustave Roussy and Centre Oscar Lambret, as well as professor of oncology at Paris-Saclay University in France.

What was the rationale for the PEACE-2 study?

The PEACE-2 trial was designed to address treatment intensification strategies for men with very high-risk localized prostate cancer. This population historically is defined by the presence of 2 or more high-risk features, including clinical stage T3 or T4 disease, Gleason score 8 to 10, or prostate-specific antigen (PSA) levels greater than 20 ng/mL, in the absence of detectable metastatic spread on conventional imaging and without pelvic nodal involvement.

“[At the time of trial development] the main SOC was, and probably still is, radiation therapy combined with long-term ADT,” Fizazi explained. “There was debated role of pelvic radiation therapy as taxanes emerged as potential options for these men. More recently, discrepancies in outcomes were reported with androgen receptor pathway inhibitors in the [phase 3] STAMPEDE [NCT00268476] and ENZARAD [ANZUP 1303; NCT02581970] trials.”

What was the design of PEACE-2?

PEACE-2 enrolled patients at least 18 years of age and no older than 75 years of age who had histologically confirmed adenocarcinoma of the prostate and met at least 2 of the criteria for high-risk defined above.² Patients were also required to have no clinically or radiologically suspected metastases, including no enlarged pelvic lymph nodes; a Gleason score of 6 or greater; no prior exposure to treatment for prostate cancer except lymph node dissection or ADT started up to 6 weeks before randomization; and an ECOG performance status of 0 or 1.

A total of 761 patients were accrued across 4 countries in the European Union between 2013 to 2021, and were randomly assigned in a 2×2 factorial design to 1 of 4 treatment arms:¹

• Arm A: ADT, comprising either an luteinizing hormone-releasing hormone agonist or antagonist for 3 years; plus mandatory intensity-modulated radiation therapy (IMRT) to the prostate at 74 to 78 Gy with 2 Gy fractions starting 3 months after initiation of ADT (n = 189)
• Arm B: ADT plus radiotherapy to the pelvis at 46 to 50 Gy (n = 191)
• Arm C: Radiotherapy to the prostate; and intravenous (IV) cabazitaxel at 20 to 25 mg/m² every 3 weeks for 4 cycles, with granulocyte colony-stimulating factor treatment recommended (n = 191)
• Arm D: ADT plus radiotherapy to the pelvis and 4 cycles of cabazitaxel (n = 190)

The study’s primary end point was cPFS. Key secondary end points included PSA response at 3 months, bPFS, MFS, PCSS, OS, quality of life, biomarkers, and acute/long-term tolerance.

What baseline characteristics are important to note?

Demographic and baseline characteristics were typical for this patient population, Fizazi noted.

“[Across all 4 arms], the median age was [approximately] 67 years, [approximately] 90% of patients had T3 or T4 disease, and approximately 80% had a high Gleason score of 8 to 10,” Fizazi said, adding that “[Seventy-nine percent] of patients had 2 risk factors, and the rest had 3 risk factors.”

The median PSA level was 22 ng/mL, 23 ng/mL, 19 ng/mL, and 22 ng/mL in the ADT plus prostate radiotherapy, ADT plus pelvic radiotherapy, ADT plus radiotherapy and cabazitaxel, and ADT plus pelvic radiotherapy and cabazitaxel arms, respectively.

How did the safety profile of the cabazitaxel-containing regimen compare with SOC therapy?

In the safety population, patients who received the cabazitaxel-containing regimen (n = 369) experienced a greater incidence of grade 3/4 adverse effects (AEs) of interest than those who received ADT plus radiotherapy alone (n = 376). These included anemia (1% with SOC; 1% with cabazitaxel), neutropenia (0%; 20%), thrombocytopenia (1%; 1%), diarrhea (0%; 4%), nausea/vomiting (0%; 1%), and increased gamma glutamyl transferase levels (2%; 4%). There were 3 suspected toxicity-related deaths in the cabazitaxel arm and none in the SOC arm.

To conclude his presentation, Fizazi noted that data about pelvic radiation therapy will be reported at a later medical conference.

Disclosures: Fizazi disclosed receiving honoraria from Astellas Pharma, Bayer, Janssen, and Novartis; serving in a consulting or advisory role for Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo Europe, Janssen, Merck Sharp & Dohme, Novartis, and Pfizer; and having travel expenses paid for AstraZeneca, Bayer, Janssen, Merck Sharp & Dohme, Novartis, and Pfizer.

References

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: first results of thePEACE-2 randomized phase III trial. J Clin Oncol. 2026;44(suppl 7)LBA307. doi:10.1200/JCO.2026.44.7_suppl.LBA307
2. A phase III of cabazitaxel and pelvic radiotherapy in localized prostate cancer and high-risk features of relapse (PEACE2). ClinicalTrials.gov. Updated July 30, 2025. Accessed February 27, 2026. https://clinicaltrials.gov/study/NCT01952223