FDA Grants Priority Review to Olaparib Combination for mCRPC

The FDA granted priority review for the supplemental new drug application (sNDA) for olaparib (Lynparza) in combination with abiraterone and prednisone or prednisolone for treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC), according to a press release from AstraZeneca.¹

Olaparib is being collaboratively developed by both AstraZeneca and MSD Research Laboratories.

“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,” said Susan Galbraith, executive vice president, Oncology Research and Development, of AstraZeneca, in a press release.

Dr. Eliav Barr, senior vice president, head of Global Clinical Development and chief medical officer at MSD Research Laboratories added: “MSD is committed to developing new treatment options for patients with metastatic castration-resistant prostate cancer, a complex disease that urgently needs more therapies. We look forward to working with the FDA towards the goal of bringing a new option to patients with mCRPC with or without HRR gene mutations.”

The phase 3 PROpel (NCT03732820) provided the results which led to olaparib’s sNDA. Results showed the olaparib plus abiraterone combination reduced the risk of progression or death by 34% compared with abiraterone alone (HR, .066; 95% CI, 0.54-0.81; P < .0001). The median radiographic progression-free survival was 24.8 months with the olaparib and abiraterone combination vs 16.6 months with abiraterone alone. The combination’s safety and tolerability profile were consistent with prior clinical trial data and with what is known of the individual treatments.

Patients with mCRPC were given 300 mg of olaparib (two 150 mg tablets) twice a day, and abiraterone was given in 1000 mg doses once per day. The primary end point of the PROpel study is radiological progression-free survival, and the secondary end points include overall survival, time to first subsequent anticancer therapy or death, time to pain progression, and number of adverse events.2

To be eligible for the PROpel study, patients must have first-line mCRPC, ongoing androgen deprivation with gonadotropin-releasing hormone analogue or bilateral orchiectomy, be a candidate for abiraterone therapy with documented evidence of progressive disease, have normal organ and bone marrow function measured within 28 days prior to administration of study treatment, and an ECOG performance score of 0 or 1.

Patients were deemed ineligible if they have a known additional malignancy that has had progression or has required active treatment in the last 5 years, have myelodysplastic syndrome or acute myeloid leukemia, clinically significant cardiovascular disease, uncontrolled hypertension, or a history of uncontrolled pituitary or adrenal dysfunction.2

Olaparib has US approval for patients with HRR gene-mutated mCRPC who progressed following prior enzalutamide (Xtandi) or abiraterone treatment. It is also approved in Europe, Japan, and China for patients with BRCA-mutated mCRPC who progressed following prior therapy which included a new hormonal agent. These approval data came from the results of the phase 3 PROfound trial (NCT02987543).

_References:

_{1. Lynparza in combination with abiraterone granted Priority Review in the US for patients with metastatic castration-resistant prostate cancer. Press release. AstraZeneca; August 16, 2022. Accessed August 16, 2022. https://bit.ly/3QFtLUM}

_{2. Study on olaparib plus abiraterone as first-line therapy in men with metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated April 5, 2022. Accessed August 16, 2022. https://bit.ly/3wvsSqb}