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Improving Survival in Patients with De Novo Metastatic Prostate Cancer
Over the past decade, multiple clinical trials have demonstrated clinically meaningful improvements in overall survival (OS) for most men with newly diagnosed metastatic prostate cancer by “intensifying” androgen deprivation therapy (ADT) with the addition of drugs such as docetaxel, abiraterone, enzalutamide, and apalutamide. Now, in the phase 3, industry-supported European PEACE-1 trial, investigators evaluated further intensification — i.e., triplet therapy — and the role of local radiotherapy.
In the open-label trial, 1173 men with de novo metastatic prostate cancer were randomized to receive standard of care (SOC; ADT) alone, SOC plus radiotherapy, SOC plus abiraterone, or SOC plus radiotherapy plus abiraterone. The trial was amended after 2 years to add docetaxel to ADT as SOC. Coprimary endpoints were radiographic progression-free survival (rPFS) and OS.
Median time from diagnosis was 2.2–2.3 months; 57%–65% of patients had high-burden disease (using the CHAARTED definition). As statistical modeling indicated no interaction between radiotherapy and abiraterone, data from the abiraterone groups were pooled for analysis. Median follow-up for rPFS was 3.5 years and for OS was 4.4 years.
Patients receiving abiraterone plus SOC (with or without docetaxel or radiotherapy) demonstrated significant improvements in rPFS (adjusted hazard ratio, 0.54; P<0.0001) and OS (aHR, 0.82; P=0.030) compared with those not receiving abiraterone. Improvements in both rPFS and OS were maintained when the analysis was restricted to patients who received ADT with docetaxel. While rPFS improvement was seen in patients with low or high metastatic burden, OS was improved only in patients with high-burden disease. Of note, subsequent life-prolonging therapies were used more commonly in patients who did not receive abiraterone. The addition of abiraterone to ADT with docetaxel was not associated with increased risk of febrile neutropenia, fatigue, or neuropathy.
The recent report of the ARASENS trial, which tested the addition of darolutamide to docetaxel in a similar patient population, offers further support to the results of PEACE-1 (NEJM JW Oncol Hematol May 2022 and N Engl J Med 2022; 386:1132). While this approach may not be suitable for all patients, for the majority of those with de novo high-volume disease, discussion of the potential survival benefit from further ADT intensification is warranted.
Fizazi K et al.
Title: 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.
Source: Lancet 2022 Apr 8; [e-pub]. (Abstract/FREE Full Text)