According to a recent analysis of the phase 3 PROfound trial, the most common adverse events that occurred in patients with metastatic castration-resistant prostate cancer treated with olaparib were anemia, nausea, decreased appetite, and fatigue. The analysis also found that these adverse events were all manageable through dose modifications and supportive therapies and did not require discontinuation of the treatment.

The PROfound study enrolled a total of 386 patients with metastatic castration-resistant prostate cancer who had failed previous treatment with a new hormonal agent. Patients were randomized on a 2:1 basis to either olaparib (n = 256) or the control arm of treatment with enzalutamide or abiraterone acetate (n = 130). Treatment continued until disease progression or unacceptable toxicity. Patients in the control group who experienced radiographic disease progression were eligible to cross over to olaparib treatment (n = 83).

The primary end point for this study is radiological progression-free survival (rPFS) in the olaparib arm. Secondary outcomes included objective response rate in the olaparib arm, rPFS in all patients, time to pain progression in the olaparib arm, and overall survival (OS) in the olaparib arm.

In this analysis, safety was assessed through adverse event reporting and laboratory assessments throughout the treatment period and at a follow-up of 30 days after the last dose.

The 4 most common adverse events in the olaparib group were anemia at 50%, nausea at 43%, fatigue and asthenia at 42%, and decreased appetite at 31%. Most events were grade 1/2 and peaked within the first 2 months of treatment. Events were managed where appropriate, primarily through dose interruption or dose reduction, and many resolved within the first 6 months of treatment.

While thromboembolic disorders were not one of the most common adverse events observed, the study authors included reports of these instances due to the significant risk of venous thromboembolic events associated with continuous androgen deprivation therapy among patients with metastatic castration-resistant prostate cancer. Overall, 20 patients in the olaparib group experienced venous thromboembolic events, 2 of whom interrupted treatment and 1 of whom discontinued, compared to 4 patients in the control group. The most common thromboembolic event observed was pulmonary embolism. The study authors did stipulate that, due to factors of the study design, it is “difficult to interpret the observed imbalance of pulmonary embolism/embolic events between study groups as no causal association was established.”

Source:

Roubad G, Özgüroğlu M, Penel M, et al. Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study. Eur J Cancer. Published online May 19, 2022. doi:10.1016/j.ejca.2022.04.016.