FDA Gives Priority Review to Olaparib and Abiraterone for mCRPC Regardless of HRR Status

Priority review was given to a supplemental new drug application for olaparib (Lynparza) plus abiraterone acetate (Zytiga) and prednisone or prednisolone in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of homologous recombination repair (HRR) mutational status, according to a press release from AstraZeneca.¹

The application is based on findings from the phase 3 PROpel trial (NCT03732820) assessing the combination vs abiraterone and placebo in the first-line setting.² Data from the planned primary analysis highlighted that imaging-based progression-free survival (PFS) was significantly longer at 24.8 months in the experimental arm vs 16.6 months in the placebo arm, with the combination leading to a decreased risk of disease progression or death by 34% (HR, 0.66; 95% CI, 0.54-0.81; P <.0001). At the time of cutoff, the overall survival (OS) findings were immature (HR, 0.86; 95% CI, 0.66-1.12; P = .29).

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“There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited. Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, Lynparza with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca.

Patients were enrolled to the study regardless of HRR mutational status. The trial used 1:1 randomization, with patients receiving either 1000 mg of abiraterone once daily plus prednisone or prednisone plus 300 mg of olaparib twice daily or placebo. The primary study end point was imaging-based PFS by investigator assessment and one of the secondary end points was OS.

Olaparib has received FDA approval previously for the treatment of HRR mutation–positive mCRPC among those who have progressed following treatment with enzalutamide (Xtandi) or abiraterone and a new hormonal agent.

References

1. First PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal agent irrespective of homologous recombination repair (HRR) gene mutations. AstraZeneca. News release. August 16, 2022. Accessed August 16, 2022. https://bit.ly/3C6uuKj
2. Clarke NW, Armstrong A, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. N Engl J Med Evi. Published online June 3, 2022. doi:10.1056/EVIDoa2200043