December 21, 2022: “AstraZeneca and MSD’s Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone has been approved in the European Union for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men for whom chemotherapy is not clinically indicated.
This approval by the European Commission was based on results from the PROpel Phase III trial and follows the positive recommendation in the EU by the Committee for Medicinal Products for Human Use in November 2022.
In the trial, Lynparza in combination with abiraterone and prednisone or prednisolone, reduced the risk of disease progression or death by 34% versus abiraterone and prednisone or prednisolone (based on a hazard ratio [HR] of 0.66; 95% confidence interval [CI] 0.54-0.81; p<0.0001).
Median radiographic progression-free survival (rPFS) was 24.8 months for Lynparza plus abiraterone versus 16.6 months for abiraterone alone.
Furthermore, a 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.
Updated results from a second planned analysis presented at ESMO 2022 showed a favourable trend towards improved overall survival with Lynparza plus abiraterone versus abiraterone alone (based on HR of 0.83; 95% CI 0.66-1.03; p=0.11), however, the difference did not reach statistical significance at the time of this data cut-off (analysis at 40% data maturity).
Prostate cancer is the most common cancer in men in Europe, with an estimated 473,000 patients diagnosed and 108,000 deaths in 2020.
Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real-world.
Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.
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, said: “The results of the PROpel Phase III 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 metastatic castration-resistant prostate cancer.
Patients with this condition in the EU will now, for the first time, have the opportunity to benefit from this new treatment combination.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Many patients with metastatic castration-resistant prostate cancer are only able to receive one line of active therapy, as the disease can progress quickly.
Lynparza in combination with abiraterone has been shown to reduce the risk of disease progression by 34% versus the standard of care treatment in the PROpel trial.
Moreover, the combination of Lynparza with abiraterone as a first-line treatment expands the use of Lynparza to a broader group of metastatic castration-resistant prostate cancer patients than those treated with Lynparza alone in the second-line setting in the PROfound trial.
Today’s approval marks a significant advance toward addressing the unmet need of patients with metastatic castration-resistant prostate cancer in the EU.”
Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: “MSD is committed to developing new treatment options for patients with metastatic castration-resistant prostate cancer, a complex disease that urgently needs more therapies.
This approval by the European Commission marks another step towards delivering on that commitment and we look forward to extending the benefits of Lynparza to more patients with metastatic castration-resistant prostate cancer in the EU.”
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).
In August, supplemental New Drug Application (sNDA) for Lynparza in combination with abiraterone and prednisone or prednisolone was accepted and granted Priority Review in the US for the treatment of adult patients with mCRPC.
The Prescription Drug User Fee Act (PDUFA) date is anticipated during the first quarter of 2023.
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.
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.”