AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that LYNPARZA in combination with abiraterone and prednisone or prednisolone (abi/pred) has been approved in Japan for the treatment of adult patients with BRCA-mutated (BRCAm) castration-resistant prostate cancer with distant metastasis (mCRPC).
This approval by the Japanese Ministry of Health, Labor and Welfare was based on an exploratory subgroup analysis of the Phase 3 PROpel trial which showed that LYNPARZA plus abi/pred demonstrated clinically meaningful improvements in both radiographic progression-free survival (rPFS) (HR=0.23 [95% CI, 0.12-0.43]) and overall survival (OS) (HR=0.39 [95% CI, 0.16-0.86]) versus abi/pred alone in patients with BRCAm mCRPC. In the BRCAm subgroup (n=85), the median rPFS and median OS were not reached (NR) for patients receiving LYNPARZA plus abi/pred (95% CI, NR-NR for both rPFS and OS) compared to a median of 8.4 months (95% CI, 5.5-14.8) and 23.6 months (95% CI, 17.8-NR), respectively, for those receiving placebo plus abi/pred. As previously reported, there was a statistically significant improvement in rPFS in the full intention-to-treat (ITT) population in the PROpel trial (n=796).
The safety and tolerability of LYNPARZA plus abi/pred in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines. In the ITT population, common adverse events (AEs) in patients who received LYNPARZA plus abi/pred were anemia (45.5%), nausea (28.1%) and fatigue (27.9%).
Prostate cancer is the most common cancer in men in Japan and the sixth leading cause of cancer death in the region, with an estimated 96,400 new cases and 13,300 deaths in 2022. Despite various treatment options available, the prognosis for mCRPC remains poor, with limited treatment 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 BRCAm mCRPC. 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. Today’s approval is a major step forward for patients in Japan with BRCAm mCRPC who urgently need new first-line treatment options.”
Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck 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 BRCAm mCRPC that improve on the current standard of care.”
LYNPARZA plus abi/pred is approved in several other countries for the treatment of appropriate adult patients with mCRPC based on the PROpel trial. In the European Union (EU), LYNPARZA plus abi/pred is approved for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated, regardless of biomarker status. This combination is also approved in the U.S. for the treatment of adult patients with deleterious or suspected deleterious BRCAm mCRPC. For the U.S. indication, patients should be selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
In Japan, LYNPARZA was previously approved for patients with BRCAm mCRPC who have progressed following prior therapy that included a new hormonal agent (NHA) based on results from the Phase 3 PROfound trial. It is approved in the EU and China for the same indication, as well as in the U.S. 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. For the U.S. indication, patients are selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Source: https://www.merck.com/
