AstraZeneca and Merck’s Lynparza combination therapy receives FDA priority review in first-line prostate cancer

AstraZeneca (AZ) and Merck’s – known as MSD outside the US and Canada – Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone has been granted Priority Review by the US Food and Drug Administration (FDA) for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC), AZ announced.

The supplemental New Drug Application (sNDA) for Lynparza was based on results from the PROpel phase 3 trial, which showed Lynparza in combination with abiraterone reduced the risk of disease progression or death by 34% versus abiraterone alone.

The study – presented at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium and later published in NEJM Evidence – also demonstrated a median radiographic progression-free survival of 24.8 months for Lynparza plus abiraterone versus 16.6 for abiraterone alone.

The safety and tolerability of Lynparza in combination with abiraterone was consistent with prior clinical trials and the known profiles of the individual medicines.

Prostate cancer is the second most common cancer in male patients in the US, projected to cause around 35,000 deaths in 2022. Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real world, AZ said. Around half of patients with mCRPC may receive only one line of active treatment, with worsening benefit of subsequent therapies.

Lynparza, which is being jointly developed and commercialised by AZ and MSD, is a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor and the first targeted treatment to block DNA damage response in cells and tumours harbouring a deficiency in homologous recombination repair, such as those with mutations in BRCA1 and BRCA2, or those where deficiency is induced by other agents.

Susan Galbraith, executive vice president, oncology R&D, AZ, said: “There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited. Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, Lynparza with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease.”

The announcement follows the European Commission’s approval of Lynparza earlier this month for the treatment of patients with germline BRCA-mutated HER2-negative high-risk early breast cancer.