1. A combination of androgen deprivation therapy, docetaxel, and abiraterone (“triplet therapy”) had the best overall survival and progression-free survival outcomes.
2. Patients receiving abiraterone were more likely to develop hypertension as a severe adverse event.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Androgen deprivation therapy (ADT) with or without docetaxel is the current standard of care (SOC) for metastatic prostate cancer. This study aimed to determine the efficacy and safety of adding abiraterone plus prednisone to the current treatment regimen. Patients were randomized to receive either SOC alone, SOC plus radiotherapy, SOC plus abiraterone, or SOC plus radiotherapy plus abiraterone. No interaction was found between radiotherapy and abiraterone; therefore, all outcomes were reported as SOC plus abiraterone versus SOC without abiraterone. The study found that patients who received abiraterone had longer progression-free survival and overall survival compared to those who did not receive abiraterone. In those that received “triple therapy” (ADT, docetaxel, and abiraterone), the number of patients that had at least one severe adverse event was higher than in those who received only ADT and docetaxel. The incidence of hypertension and hepatotoxicity was also increased with abiraterone compared to without. Limitations of this study include the ongoing changes made to standard of care which differ between countries, leading to some patients receiving docetaxel and some not. Nonetheless, this study provides high-quality promising results for perhaps a future triple therapy management of metastatic prostate cancer.
In-Depth [randomized controlled trial]: This phase 3 clinical trial enrolled male patients aged 18 years or older across seven European countries with confirmed de novo metastatic prostate adenocarcinoma. 1173 patients were enrolled and randomly assigned 1:1:1:1 to receive either standard of care (SOC) (n=296), SOC plus radiotherapy (n=293), SOC plus abiraterone (n=292), or SOC plus radiotherapy plus abiraterone (n=291). SOC was defined as androgen deprivation therapy (ADT) with (n=710) or without IV docetaxel (n=462). Prednisone was given with abiraterone. Treatment was not blinded to neither investigators nor patients.
The primary outcome was radiographic progression-free survival and overall survival. No interaction was found between abiraterone and radiotherapy. Due to this, following analysis was done 2 x 2 (SOC without abiraterone with or without radiotherapy vs. SOC plus abiraterone with or without radiotherapy). Patients who received abiraterone (n=589) had longer radiographic progression-free survival (HR 0.54, 99.9% CI 0.41-0.71, p<0.0001) and overall survival (HR 0.82, p=0.030) compared to those that did not. In the ADT and docetaxel group, the percentage of patients that experienced at least one severe adverse event was 63% with abiraterone and 52% without abiraterone. However, there were less severe adverse events seen overall in the abiraterone group (49 per 100 person-years) versus those who did not (55 per 100 person-years). There was a greater number of patients that experienced hypertension (22% vs. 13%) and hepatoxicity (6% vs. 1%) in those that received abiraterone compared to those who did not. Otherwise, the events were similar between the two groups.
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