European Commission Approves Olaparib Combinations for mCRPC

Olaparib in combination with abiraterone and prednisone or prednisolone alone has been approved as treatment for metastatic castration-resistant prostate cancer in the European Union.

The European Commission has granted approval to olaparib (Lynparza) in combination with abiraterone acetate (Zytiga) and prednisone or prednisolone alone as treatment for adult patients with metastatic castration-resistant prostate cancer (mCRPC) for whom chemotherapy is not clinically indicated, according to a press release from AstraZeneca and Merck.1

The approval was supported by findings from the phase 3 PROpel trial (NCT03732820), which indicated that olaparib plus abiraterone and prednisone or prednisolone yielded a 34% reduction in risk of disease progression or death compared with placebo plus abiraterone (HR, 0.66; 95% CI, 0.54-0.81; P <.0001). Additionally, the median radiographic progression-free survival (rPFS) was 24.8 months (95% CI, 20.5-27.6) among patients receiving olaparib vs 16.6 months (95% CI, 13.9-19.2) for patients in the placebo cohort.

A planned sensitivity analysis by blinded independent central review highlighted a median rPFS of 27.6 months and 16.4 months in the olaparib and placebo arms, respectively. The secondary end point of overall survival in the PROpel trial was 37.1% in the olaparib arm vs 43.1% in the placebo arm, although statistical significance was not reached (HR, 0.83; 95% CI, 0.66-1.03).

“The results of the phase 3 PROpel trial of olaparib in combination with abiraterone as a first-line treatment show that this therapeutic combination can provide significant clinical benefit to patients with mCRPC,” Noel Clarke, MBBS, FRCS, ChM, senior investigator of the PROpel trial, urological surgeon, and professor of urological oncology at Manchester’s Christie/Salford Royal Hospitals and Manchester University, said in the press release. “Patients with this condition in the European Union will now, for the first time, have the opportunity to benefit from this new treatment combination.”

Previously, the FDA gave priority review to a supplemental application for olaparib plus abiraterone in mCRPC regardless of homologous recombination repair mutational status in August 2022.2 The regulatory decision was also based on findings from the phase 3 PROpel trial.

References

  1. LYNPARZA® (olaparib) in combination with abiraterone and prednisone or prednisolone approved in the EU as treatment for certain patients with metastatic castration-resistant prostate cancer. News release. AstraZeneca, Merck. December 21, 2022. Accessed December 21, 2022. bit.ly/3v6ghIy
  2. 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 December 21, 2022. https://bit.ly/3C6uuKj