AZ/Merck & Co take on Clovis as FDA approves prostate cancer drug

The FDA has approved AstraZeneca and Merck & Co’s Lynparza (olaparib) in metastatic castration-resistant prostate cancer, just days after the regulator gave the nod for Clovis’ PARP-class rival Rubraca. 

While Clovis stole a march on its big pharma rival by just a few days, Lynparza has the advantage of approval in a wider patient group and already has wide reimbursement coverage in the US. 

Lynparza’s FDA label covers men with metastatic castration-resistant prostate cancer and homologous recombination repair (HRR) mutations, after treatment with Pfizer/Astellas Xtandi (enzalutamide) or Johnson & Johnson’s Zytiga (abiraterone). 

While Rubraca’s indication in BRCA1/2 mutated cancers covers around 12% of mCRPC patients, Lynparza’s label covers BRCA and several other similar mutations. 

This wider label means that it could be used in between 20-30% of the patient group, plus has the advantage of the clout of the two big pharma companies, who signed a strategic oncology agreement based around Lynparza in 2017. 

Approval was based on findings of the PROfound trial, which showed Lynparza reduced risk of disease progression or death by 66% compared with Xtandi or Zytiga in men with BRCA 1/2 mutations. 

Radiographic progression-free survival (rPFS) was a median of 7.4 months in those treated with Lynparza, compared with 3.6 months with Zytiga or Xtandi. 

Lynparza also showed an rPFS benefit in the overall HRR gene-mutated trial population, a key secondary endpoint, and reduced the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months versus 3.5 months with Zytiga or Xtandi. 

There was also an overall survival benefit compared with Xtandi or Zytiga in men with BRCA1/2 or ATM mutations – Lynparza reduced the risk of death by 31% and improved OS to a median of 19.0 months versus 14.6 months with either of the other two drugs. 

EU and other global regulators are also reviewing Lynparza in this indication, and AZ and Merck & Co, known as MSD outside the US and Canada, are testing Lynparza in additional trials in metastatic prostate cancer.

These include the ongoing phase 3 PROpel trial as a first line treatment in combination with abiraterone acetate for patients with mCRPC versus Zytiga alone.