AstraZeneca's Lynparza plus abiraterone approved in Japan for treatment of BRCA-mutated metastatic castration-resistant prostate cancer

This approval by the Japanese Ministry of Health, Labour and Welfare was based on a subgroup analysis of the PROpel Phase III trial which showed that Lynparza plus abiraterone demonstrated highly clinically meaningful improvements in both radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone alone in patients with BRCA mutations.

Prostate cancer is the most common cancer in men in Japan and the sixth leading cause of cancer death in the region. Despite various treatment options available, the prognosis for mCRPC remains poor, with limited options for patients whose cancer progresses following initial treatment.

Mototsugu Oya, Professor and Chairman, Department of Urology, Keio University School of Medicine, Japan, said, “The PROpel trial showed that the combination of Lynparza plus abiraterone delivered clinically meaningful improvements in outcomes for patients with BRCA-mutated metastatic castration-resistant prostate cancer. With this approval, patients in Japan will now have the opportunity to benefit from this new treatment combination which has the potential to become the new standard of care for patients with BRCA mutations.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said, “This Lynparza combination has been shown to reduce the risk of disease progression or death compared to standard of care and underscores the critical importance of BRCA testing at metastatic diagnosis. This approval is a major step forward for patients in Japan with BRCA-mutated metastatic castration-resistant prostate cancer who urgently need new first-line treatment options.”

Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said, “Prostate cancer impacts thousands of patients in Japan each year, and currently there are limited options available to those with metastatic disease. It is very important to develop and deliver novel treatment combinations to patients with BRCA-mutated metastatic castration-resistant prostate cancer that improve on the current standard of care.”

In the subgroup analysis of PROpel, results showed that Lynparza plus abiraterone reduced the risk of disease progression or death by 77% (based on a hazard ratio [HR] of 0.23; 95% confidence interval [CI] 0.12-0.43) and reduced the risk of death by 61% (based on a HR of 0.39; 95% CI 0.16-0.86) versus abiraterone alone in patients with BRCAm mCRPC. Median rPFS and median OS were not reached for patients treated with Lynparza plus abiraterone versus a median of 8.4 months and 23.6 months, respectively, for those treated with abiraterone alone.

The safety and tolerability of Lynparza plus abiraterone in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines.

Lynparza in combination with abiraterone and prednisone or prednisolone is approved in the European Union (EU) and several other countries for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated, based on the PROpel trial. This combination is also approved in the US for the treatment of adult patients with deleterious or suspected deleterious BRCAm mCRPC.

Read also: USFDA nod to AstraZeneca, MSD's Lynparza plus Abiraterone and Prednisone or Prednisolone for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

Lynparza monotherapy is also approved in Japan for patients with BRCAm mCRPC based on results from the PROfound Phase III trial. It is approved in the EU and China for the same indication, as well as in the US 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.