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FDA Approves Lynparza With Myriad, Foundation Med CDx Tests in HRR-Mutated Prostate Cancer

NEW YORK – The US Food and Drug Administration on Wednesday announced the approval of AstraZeneca and Merck's olaparib (Lynparza) for metastatic castration-resistant prostate cancer patients with homologous recombination repair deficiency.

The agency simultaneously also approved two companion diagnostics that may be used to identify best responders to this drug: Myriad Genetics' BRACAnalysis CDx to identify patients with germline BRCA1/2 mutations, and Foundation Medicine's FoundationOne CDx to identify patients with HRR-mutated genes.

The FDA based its decision on the results of the Phase III PROfound trial, which included men with BRCA1/2 or ATM gene mutations in one cohort and patients with mutations in 12 other genes associated with the HRR pathway in another cohort. HRR deficiency can result from mutations in BRCA1/2 and other genes involved in DNA repair processes. Between 20 percent and 30 percent of metastatic castration-resistant prostate cancer patients have HRR gene mutations.

In PROfound, patients with mutations in BRCA1/2 or ATM on olaparib had a median radiographic progression-free survival of 7.4 months versus 3.6 months with enzalutamide (Pfizer/Astellas Xtandi) or abiraterone (Janssen's Zytiga). In the overall HRR-mutated population, median radiographic progression-free survival was 5.8 months for those receiving olaparib versus 3.5 months on those on enzalutamide or abiraterone.

More recent data from the PROfound study showed that BRCA1/2- and ATM-mutated patients had a median overall survival of 19 months on olaparib, compared to 14.6 months with the comparator drugs.

"Prostate cancer has lagged behind other solid tumors in the era of precision medicine," Maha Hussain from Northwestern University, who was a principal investigator of PROfound, said in a statement. She added that the latest approval "brings a molecularly targeted treatment to men with HRR gene-mutated metastatic castration-resistant prostate cancer in the US."

As a result of this approval, AstraZeneca will receive a $35 million milestone payment from Merck. This same indication is currently under review with regulators in Europe and other countries.

Last week, the FDA approved Clovis Oncology's rucaparib (Rubraca) for men with BRCA1/2-mutated, metastatic castration-resistant prostate cancer who have previously received androgen receptor-directed therapy and taxane-based chemotherapy. Clovis collaborated with Foundation Medicine to use its NGS panel in the TRITON2 study to identify patients with alterations in BRCA1/2, ATM, and in 13 other genes indicating homologous recombination deficiency.