Capivasertib plus docetaxel continued to show an improvement in overall survival compared with docetaxel alone in patients with metastatic castration-resistant prostate cancer.
Capivasertib plus docetaxel continued to show an improvement in overall survival (OS) compared with docetaxel alone in patients with metastatic castration-resistant prostate cancer (mCRPC), according to results from an updated analysis of the phase 2 ProCAID trial (NCT02121639) that were presented in a poster at the 2022 Genitourinary Cancers Symposium.1
The median OS in patients who received capivasertib plus docetaxel was 25.3 months vs 20.3 months in patients who received placebo plus docetaxel (HR, 0.70; 95% CI, 0.47-1.05; P = .09). Subsequent life-extending treatment options and unbalanced baseline factors did not appear to influence this OS benefit.
“The primary analysis [of the ProCAID trial] showed no difference between treatment arms for the primary end point of composite progression-free survival (PFS). However, OS, which was a secondary end point, was extended in the capivasertib plus docetaxel arm. We report an updated analysis of mature OS data, which was planned once events had reached [at least] 65%,” lead study author Simon J. Crabb, BSc, MBBS, MRCP, PhD, associate professor in medical oncology within medicine at the University of Southampton and associate clinical director of the Southampton Clinical Trials Unit, and colleagues, wrote.
The PI3K/AKT/PTEN pathway is often deregulated in mCRPC. The ProCAID trial was a randomized, double-blind trial which looked at the effects of adding capivasertib, a selective AKT isoform inhibitor, to docetaxel in patients with mCRPC. This investigative arm was compared with a control arm that received placebo plus docetaxel. A total of 150 patients were randomized across the 2 arms.
The updated analysis looked at mature OS data, as well as OS outcomes within treatment subsets. OS was calculated in the intention-to-treat (ITT) population using a Cox proportional hazards model that was adjusted for the minimization factors of visceral metastases, bone metastases, investigational site, and prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga).
This update also investigated unadjusted OS outcomes within subsets based on prior exposure to abiraterone and/or enzalutamide, and the balance of post-trial, life-extending treatment use between the treatment arms.
At the time of the OS update, 66% of patients (n = 99) had died, with 88.9% of these deaths (n = 88) occurring from prostate cancer. In total, 1 patient (0.7%) remained on placebo or capivasertib. At this extended follow-up, investigators saw no clinically significant differences from previously reported safety outcomes.
Of the ITT population, 99% of patients had received at least 1 subsequent life-extending treatment option, such as enzalutamide, radium-223 dichloride (Xofigo), cabazitaxel (Jevtana), and abiraterone. These treatments were balanced between the 2 trial arms and were administered to 68% of patients in the investigative arm vs 64% of patients in the placebo arm. Additionally, 101 patients (67.3%; capivasertib, n = 51; placebo, n = 50) had received abiraterone or enzalutamide prior to randomization.
Within the subgroup of patients who had received abiraterone or enzalutamide prior to enrollment in the trial, an exploratory analysis found that the OS benefit for the investigative arm was maintained, with a median OS of 25 months (95% CI, 17.7-31.1) vs 17.6 months (95% CI, 14.4-20.3) in the placebo arm (HR, 0.57; 95% CI, 0.36-0.91). However, the OS benefit in the investigative arm was not observed in the 49 patients who had not received prior abiraterone or enzalutamide. In these patients, the median OS was 31.1 months (95% CI, 20.1-41.1) in the investigative arm and was not reached ([NR] 95% CI, 22.7-NR) in the control arm (HR, 1.43; 95% CI, 0.63-3.23).
This updated analysis showed OS was consistent regardless of biomarker status for PI3K/AKT/PTEN pathway activation, results which were previously reported in the primary analysis as well.
Further investigation is necessary to define the clinical benefits of this approach.