Lynparza (olaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor.
Lynparza is specifically indicated for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone.
Lynparza is supplied as a tablet for oral administration. The recommended dosage of Lynparza is 300 mg taken orally twice daily, with or without food until disease progression or unacceptable toxicity. Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
The FDA approval of Lynparza for adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone was based on the phase 3 PROFOUND trial. Results from the PROfound trial showed Lynparza reduced the risk of disease progression or death by 66% and improved radiographic progression-free survival (rPFS) to a median of 7.4 months vs. 3.6 months with enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations, the primary endpoint and a subpopulation of HRR gene mutations. Results also showed Lynparza reduced the risk of radiographic disease progression or death by 51% and improved rPFS to a median of 5.8 months vs. 3.5 months with enzalutamide or abiraterone in the overall trial population of men with HRR gene-mutated mCRPC, a key secondary endpoint. Additional results showed a statistically significant improvement in the key secondary endpoint of overall survival (OS) with Lynparza vs. enzalutamide or abiraterone in men with mCRPC and BRCA1/2 or ATM gene mutations. Results showed Lynparza reduced the risk of death by 31% and improved OS to a median of 19.1 months vs. 14.7 months for those treated with enzalutamide or abiraterone.
Adverse effects associated with the use of Lynparza may include, but are not limited to, the following:
Lynparza is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.
For additional information regarding Lynparza or pancreatic cancer please visit the Lynparza web page.