How Lynparza works
It 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.
Lynparza received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) as a treatment for people with BRCA1/2, or ATM-mutated metastatic castration-resistant prostate cancer (mCPRPC), who previously received chemotherapy and at least one hormonal treatment agent.
Lynparza in clinical trials
In vitro studies have shown that the toxic effect on cells may be through the inhibition of the activity of PARP, increasing the formation of PARP-DNA complexes, leading to cell death.
In a Phase 2 clinical trial named TOPARP-A (NCT01682772), 49 men with mCPRPC responded to Lynparza treatment. Biopsies of their tumors showed an almost perfect association between clinical response to Lynparza and DNA deficiencies. A total of 16 participants responded to the treatment, 14 of whom had DNA deficiencies, representing a response rate of 88 percent. The duration of the response was 40 weeks, and progression-free survival was 9.8 months in the group with DNA damage and 2.7 months in the group with normal DNA.
A Phase 3 study (NCT02987543) to assess the safety and effectiveness of Lynparza versus two other prescription medicines used to treat prostate cancer, Xtandi (enzalutamide) or Zytiga (abiraterone acetate) in men with mCPRPC who have failed prior treatment, is currently recruiting participants.
The primary objective of the trial is a change in progression-free survival. Secondary objectives include overall survival, progression without pain, and confirmed response rate. AstraZeneca expects to enroll 340 participants and the estimated completion date of the study is February 2021.
The combination of Lynparza with other anti-cancer agents that decrease the activity of bone marrow may prolong the toxic effect of the drug.
The most common adverse reactions caused by Lynparza recorded in clinical studies include anemia, nausea, fatigue, gastric problems, headache, muscle pains, dermatitis, and abdominal discomfort.
Lynparza has been approved in 40 countries for the treatment of women with BRCA-mutated ovarian cancer. AstraZeneca is investigating the use of Lynparza in other PARP-dependent tumors, such as mCPRPC.
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