FDA Approves Olaparib Combination to Treat BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

The FDA today approved olaparib (Lynparza) when used in combination with abiraterone and prednisone or prednisolone to treat adult patients with BRCA-mutated (BRCAm) metastatic castration resistant prostate cancer (mCRPC).

The action was jointly announced by AstraZeneca and Merck and Co, known internationally as MSD.

The action follows an exploratory subgroup analysis from the PROpel phase 3 trial, which showed that olaparib with abiraterone showed a clinically meaningful improvement in radiographic progression-free survival (PFS) (HR, 0.24; 95% CI, 0.12-0.45) and overall survival (OS) (HR, 0.30; 95% CI, 0.15-0.59) compared with abiraterone alone in patients who have BRCA mutations.

Median radiographic PFS and OS were not reached for patients taking olaparib with abiraterone vs a median 8 and 23 months, respectively, for those taking abiraterone alone.

Prostate cancer is the second most common cancer in men, and 5-year survival rates remain low. Among patients with mCRPC, about 10% have BRCA mutations; these patients have an even worse prognosis, with most unlikely to live beyond 3 years, which is the typical OS in a clinical trial setting.

“Preventing or delaying radiographic progression or death is an important clinical end point in assessing cancer treatment and is very important to patients, their caregivers, and their families,” said trial investigator Andrew Armstrong, MD, ScM, of the Duke Cancer Institute, in a statement. “The PROpel results showed the [olaparib] 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.”

“There is a critical unmet need for new first-line treatment options for patients with BRCA-mutated metastatic castration-resistant prostate cancer and this approval underscores the importance of BRCA testing at metastatic diagnosis,” added Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca. “We look forward to bringing the benefit of this [olaparib] combination to patients earlier in their treatment.”

Eliav Barr, senior vice president, head of global clinical development and chief medical officer, MSD Research Laboratories, said, “It is imperative that we create new ways to treat advanced cancers and help improve patient outcomes by building on the current standard of care.” This approval, he added, “reinforces the importance of routine testing for genetic mutations at metastatic diagnosis to help guide clinical decisions.”

Olaparib in combination with abiraterone and prednisone or prednisolone is approved in the European Union and several other countries, and olaparib is approved in the United States for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCAm and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone.

Reference

Lynparza (olaparib) plus abiraterone approved in the US for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer. News release. BusinessWire. June 1, 2023. Accessed June 1, 2023. https://tinyurl.com/5n7zxfe8