Lynparza (olaparib) is an oral maintenance treatment, approved that the U.S. Food and Drug Administration (FDA) for men with metastatic castration-resistant prostate cancer (mCRPC) who carry mutations in homologous recombination repair (HRR) genes, including BRCA or ATM.

The approval is specifically for men who failed to respond to prior treatment with Xtandi (enzalutamid) or Zytiga (abiraterone acetate), two hormone therapies. The FDA based its decision on results from the Phase 3 PROfound trial.

AstraZeneca and Merck (known as MSD outside of North America) jointly manufacture Lynparza.

How does Lynparza work?

Lynparza is a poly ADP-ribose polymerase (PARP) inhibitor. PARP is an enzyme that repairs damaged DNA. It also plays an important role in DNA replication, recombination, and transcription. Blocking the activity of PARP increases the sensitivity of tumor cells to cancer treatments.

In vitro studies have shown that its toxic effect on cells may be through the inhibition of PARP activity, increasing the formation of  PARP-DNA complexes, leading to cell death.

Lynparza in clinical trials

In a Phase 2 clinical trial named TOPARP-A (NCT01682772), 49 men with mCPRPC were treated with Lynparza, and 16 responded to treatment; 14 of them had DNA deficiencies. Biopsies of their tumors showed an almost perfect association between clinical response to Lynparza and DNA deficiencies.While patients’ overall response rate was about 33%, the response of cancers with relevant mutations was 88%. Progression-free survival was 9.8 months in the group with DNA damage, and 2.7 months in the group with no DNA damage.

The PROfound Phase 3 study (NCT02987543) compared the safety and effectiveness of Lynparza to Xtandi and Zytiga in men with mCPRPC whose disease progressed while on these hormone treatments. Results showed that the largest benefit occurred in patients with mutations in the BRCA1BRCA2, and ATM genes. (These are the most common HRR gene mutations.) Those taking Lynparza lived significantly longer without seeing their cancer worsen — a median of 7.4 months versus 3.6 months in men given Xtandi or Zytiga. This corresponded to a 66% lower risk of disease progression or death.

Researchers also saw a clinical benefit in the overall population of men with HRR-mutated tumors, where Lynparza reduced such risk by 51%. It also improved progression-free survival to a median of 5.8 months versus 3.5 months in men treated with Xtandi or Zytiga.

Other information

The combination of Lynparza with other anti-cancer agents that decrease the activity of bone marrow may prolong the toxic effects of the therapy.

The most common adverse reactions that researchers recorded in clinical studies included anemia, nausea, fatigue, gastric problems, headache, muscle pains, dermatitis, and abdominal discomfort.

Patients with advanced ovarian cancer, metastatic breast cancer, and metastatic pancreatic cancer can also use Lynparza.


Last updated: May 22, 2020


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