Dr Childs on Treatment With Olaparib Plus Abiraterone in mCRPC

Dan S. Childs, MD, medical oncologist, Mayo Clinic, discusses first-line olaparib (Lynparza) plus abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer (mCRPC) as evaluated in the phase 3 PROpel trial (NCT03732820).

PROpel is a pivotal clinical trial designed to investigate the efficacy of olaparib in men with mCRPC who were initiating treatment following progression on androgen deprivation therapy, Childs begins. Notably, patients were enrolled irrespective of their homologous recombination repair (HRR) status, he notes. The trial employed a randomization process, assessing patients in a 1:1 ratio to receive either olaparib or placebo plus abiraterone, a standard treatment for mCRPC, Childs explains.

The primary end point of the study was radiographic progression-free survival (PFS), he continues. Additionally, overall survival (OS) was monitored as a secondary end point, Childs adds. Initial analysis of the trial results revealed an improved PFS among patients receiving olaparib compared with those receiving placebo, he imparts. However, a deeper dive into the data through subsequent analyses unveiled intriguing findings regarding the differential responses to olaparib based on genetic profiles, Childs reports.

Specifically, it was observed that the therapeutic benefit of olaparib was most pronounced in patients harboring alterations in the 

 genes, who represented approximately 11% of the total trial population, he continues, adding that this subgroup experienced a substantial reduction in the risk of disease progression or death. Conversely, patients lacking 

 alterations seemed to derive less pronounced benefits from olaparib treatment, highlighting the importance of genetic biomarkers in guiding personalized therapeutic decisions, Childs explains. These findings underscored the significance of molecular profiling in identifying patients who are most likely to benefit from targeted therapies such as olaparib.

Based on the evidence derived from the PROpel trial, in May 2023, the combination of 

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Dan S. Childs, MD, discusses treatment with olaparib and abiraterone in metastatic castration-resistant prostate cancer.

Dr Childs on Treatment Updates in mHSPC

Dan S. Childs, MD, medical oncologist, Mayo Clinic, discusses the evolution of the treatment armamentarium for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Historically, most patients with mHSPC have received doublet therapies, either androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) or ADT plus docetaxel, Childs says. In 2022, however, positive findings from the phase 3 ARASENS (NCT02799602) and PEACE-1 (NCT01957436) trials were published, which changed the mHSPC treatment landscape, Childs notes. ARASENS compared the triplet regimen of ADT plus docetaxel and darolutamide (Nubeqa) to the doublet regimen of ADT plus docetaxel. In this trial, treatment with the triplet regimen elicited a 32.5% reduction in the risk of death vs the doublet regimen (HR, 0.68; 95% CI, 0.57-0.80; 

 < .001). PEACE-1 compared the triplet regimen of ADT plus docetaxel and abiraterone to the doublet regimen of ADT plus docetaxel. In this trial, treatment with the triplet regimen led to a substantial reduction in the risk of death compared with the doublet regimen.

Although the findings from ARASENS and PEACE-1 were meaningful, they also spurred questions regarding the value that docetaxel adds to ADT and ARPI treatment backbones, Childs explains. However, this question may be difficult to answer, as no studies have been planned or conducted to compare the ARASENS and PEACE-1 triplet regimens with ARPI-based doublet regimens, Childs emphasizes.

 Institutional Perspectives in Cancer webinar on genitourinary cancers, Childs and colleagues discussed data from a study conducted by Irbaz Bin Riaz, MBBS, MS, of Mayo Clinic, who conducted a mixed-method systematic review and meta-analysis of triplet regimens vs ARPI-based doublet regimens. This meta-analysis found that patients with de novo, high-volume mHSPC derive the most benefit from the addition of docetaxel to ADT and an ARPI, according to Childs. However, the oncologic benefit derived from receiving docetaxel early in the treatment course may be low for patients in other risk subgroups and not worth the risk of developing chemotherapy-associated adverse effects, Childs concludes.

Dan S. Childs, MD, discusses the evolution of the treatment armamentarium for patients with metastatic hormone-sensitive prostate cancer.

Dan S. Childs, MD

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Dr Childs on Treatment With Olaparib Plus Abiraterone in mCRPC

Dr Childs on Treatment Updates in mHSPC