FDA Approves Olaparib Plus Abiraterone, Prednisone for Metastatic Castration-Resistant Prostate Cancer


Investigators previously reported a statistically significant improvement in radiographic progression-free survival in the full intention-to-treat population of adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer.

The FDA has approved olaparib (Lynparza; AstraZeneca and Merck) in combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).

Image Credit: Adobe Stock - Dr_Microbe

Image Credit: Adobe Stock - Dr_Microbe

In the United States, prostate cancer is the second most common cancer in men. Despite an increase in available therapies for patients with mCRPC, the 5-year survival rate remains low.

Many patients with mCRPC are only able to receive 1 line of therapy as the disease progresses quickly. Furthermore, approximately 10% of patients with mCRPC will have BRCA mutations, which are associated with a poor prognosis and worse outcomes.

“There is a critical unmet need for new first-line treatment options for patients with BRCA-mutated mCRPC, and this approval underscores the importance of BRCA testing at metastatic diagnosis,” said Dave Fredrickson, executive vice president of the oncology business unit at AstraZeneca, in a press release. “We look forward to bringing the benefit of this Lynparza combination to patients earlier in their treatment.”

The approval was based on an exploratory subgroup analysis from the phase 3 PROpel trial, which showed that olaparib plus abi/pred demonstrated clinically meaningful improvements in both radiographic progression-free survival (rPFS) and overall survival (OS) versus abi/pred alone in patients with BRCA-mutated mCRPC. The trial tested the efficacy, safety, and tolerability of olaparib versus placebo in addition to abi/pred in 796 patients with mCRPC who had not received prior chemotherapy or new hormonal agents in the mCRPC setting.

In the BRCA-mutated subgroup, the median rPFS and OS were not reached among those receiving the combination, compared to a median of 8 months rPFS and 23 months OS in those receiving placebo plus abi/pred.

Investigators had previously reported a statistically significant improvement in rPFS in the full intention-to-treat population of the PROpel trial. Based on an exploratory analysis of rPFS and OS in the BRCA-mutated and non-BRCA-mutated subgroups, FDA officials concluded that the improvement in the intent-to-treat population was primarily attributed to the results seen in the subgroup of patients with BRCA mutations.

“Preventing or delaying radiographic progression is an important clinical endpoint in assessing cancer treatment and is very important to patients, their caregivers, and their families,” said PROpel investigator Andrew Armstrong, MD, ScM, in the press release. “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 mCRPC.”

In the intent-to-treat population, the most common adverse events (AEs) in patients who received olaparib plus abi/pred were anemia (48%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia and dizziness (14% each), and abdominal pain (13%). Among those who received olaparib in combination with abi/pred, 16% permanently discontinued treatment with olaparib due to an AE, 48% had a dosage interruption of olaparib, and 21% had a dose reduction.

In the United States, olaparib was previously approved for patients with homologous recombination repair gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone, based on data from the phase 3 PROfound trial.

“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,” said Eliav Barr, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release. “In PROpel, the Lynparza combination improved rPFS and OS for the subgroup of patients with BRCA-mutated mCRPC. This approval reinforces the importance of routine testing for genetic mutations at metastatic diagnosis to help guide clinical decisions.”


FDA Approves Lynparza (olaparib) Plus Abiraterone and Prednisone or Prednisolone for Treatment of Adult Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC). News release. Merck. June 1, 2023. Accessed June 1, 2023. https://www.merck.com/news/fda-approves-lynparza-olaparibplus-abiraterone-and-prednisone-or-prednisolone-for-treatment-of-adult-patients-with-brca-mutated-metastatic-castration-resistant-prostate-cancer-mcrpc/

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