FDA Clears Lynparza for Prostate Cancer with High Mortality Risk

The FDA granted another prostate cancer indication to AstraZeneca and Merck’s Lynparza (olaparib). It is now approved in combination with abiraterone and prednisone or prednisolone for patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).

Lynparza is already approved in the United States as monotherapy for patients with homologous recombination repair (HRR) gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.

Mohit Manrao

The wholesale acquisition cost (WAC) of a 150 mg tablet, 30-day supply of Lynparza is $15,886.92, Mohit Manrao, senior vice president, head of US Oncology for AstraZeneca, told Formulary Watch.

“Prostate cancer is a devastating disease and the number of patients predicted to die from prostate cancer is expected to double in the next 20 years (from 375,000 in 2020 to 720,000 in 2040),” Manrao said.

Metastatic castration-resistant prostate cancer, in particular, carries a poor prognosis as many patients with mCRPC do not live beyond three years, Manrao added. “Despite treatment options, about half of mCRPC patients in the United States receive only one line of active therapy. This highlights the need for more efficacious treatment options in the first-line setting. The FDA approval brings the benefit of Lynparza and abiraterone combination to BRCA-mutated patients earlier in their treatment journey.”

The current mCRPC treatment approach is often the use of a novel hormonal agent (NHA) (abiraterone or enzalutamide) followed by retreatment with another NHA or chemotherapy at disease, according to Manrao.

With the new indication, patients will need to undertake a biomarker test to determine status before they are approved for this combination therapy, according to Manrao. “For all patients with mCRPC — including those with BRCA gene mutations — biomarker testing is important to help identify familial risk, treatment options and responses to targeted therapies,” he said.

The approval was based on a subgroup analysis of the phase 3 PROpel 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.

The Lynparza combination reduced the risk of disease progression or death by 76% and reduced the risk of death by 70% versus abiraterone alone, Manrao said.

Preventing or delaying radiographic progression or death is an important clinical endpoint in assessing cancer treatment and is very important to patients, their caregivers, and their families,” said Andrew Armstrong, M.D., with the Duke Cancer Institute, Durham, North Carolina, US, and an investigator in the PROPel trial. “The PROpel results showed the Lynparza combination demonstrated a notable clinically meaningful benefit that should rapidly be considered as the standard of care treatment for patients with BRCA-mutated metastatic castration-resistant prostate cancer."

Median rPFS and median OS were not reached for patients treated with Lynparza plus abiraterone versus a median of 8 months and 23 months, respectively, for those treated with abiraterone alone. The safety and tolerability profile of Lynparza plus abiraterone in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines, AstraZeneca said.

Lynparza in combination with abiraterone and prednisone or prednisolone is approved in the European Union and several other countries to treat patients with mCRPC based on the PROpel trial.