Lynparza combination approved in EU for advanced prostate cancer

The European Commission (EC) has approved Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone for metastatic castration-resistant prostate cancer (mCRPC) in male adults in the European Union for whom chemotherapy is not clinically indicated, making it the first approved poly(ADP-ribose) polymerase (PARP) inhibitor to demonstrate clinically meaningful benefits in combination with a new hormonal agent.

Noel Clarke, Urological Surgeon and Professor of Urological Oncology at Manchester’s Christie/Salford Royal Hospitals and Manchester University, a senior investigator of the PROpel trial, commented: “Patients with this condition in the EU will now, for the first time, have the opportunity to benefit from this new treatment combination.”

Positive Phase III trial results for metastatic castration-resistant prostate cancer

The approval was based on results from the PROpel Phase III trial (NCT03732820) which showed Lynparza in combination with abiraterone extended median radiographic progression-free survival benefit beyond two years in this setting.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca stated that the EC’s approval is important because: “Many patients with metastatic castration-resistant prostate cancer are only able to receive one line of active therapy, as the disease can progress quickly.”

The EC’s approval follows the positive recommendation in the EU by the Committee for Medicinal Products for Human Use (CHMP) in November 2022.

In the PROpel Phase III trial, Lynparza in combination with abiraterone and prednisone or prednisolone demonstrated:

• A reduced risk of disease progression or death by 34 percent versus abiraterone and prednisone or prednisolone (based on a hazard ratio [HR] of 0.66; 95 percent confidence interval [CI] 0.54-0.81; p<0.0001)
• Median radiographic progression-free survival (rPFS) of 24.8 months for Lynparza plus abiraterone versus 16.6 months for abiraterone alone
• Planned rPFS analysis by blinded independent central review (BICR) showed Lynparza plus abiraterone had a median rPFS of 27.6 months compared to 16.4 months with abiraterone alone, extending median rPFS by almost one year.

The safety and tolerability of Lynparza in combination with abiraterone in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines. There was no increase in the rate of discontinuation of abiraterone in patients treated with Lynparza in combination with abiraterone and no detrimental effect on health-related quality of life versus those treated with abiraterone alone (Functional Assessment of Cancer Therapy-Prostate questionnaire).

Updated results also showed a favourable trend in improved overall survival with Lynparza plus abiraterone versus abiraterone alone, however the difference did not reach statistical significance at the time of this data cut-off (analysis at 40 percent data maturity).

Following this approval for Lynparza in the EU, AstraZeneca will receive a regulatory milestone payment from MSD of $105m, anticipated to be booked as Collaboration Revenue by the Company during the fourth quarter of 2022.

Current approvals of Lynparza

Lynparza is approved in the US based on results from the PROfound Phase III trial as monotherapy for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCA and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan, and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent.