Currently Enrolling Trials
Lynparza (olaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor.
Lynparza is specifically indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
Lynparza is supplied as a tablet for oral administration. The recommended dose is 300 mg taken orally twice daily, with or without food until disease progression or unacceptable toxicity.
The FDA approval of Lynparza for pancreatic cancer was based on POLO, a double-blind, placebo-controlled, multi-center trial that randomized (3:2) 154 patients with gBRCAm metastatic pancreatic adenocarcinoma to olaparib 300 mg orally twice daily or placebo until disease progression or unacceptable toxicity. The main efficacy outcome measure was progression-free survival (PFS) by blinded independent central review using RECIST 1.1. Additional efficacy outcome measures were overall survival (OS) and overall response rate (ORR). Median PFS was 7.4 months for patients who received olaparib compared with 3.8 months for patients who received placebo. Median OS for olaparib and placebo was 18.9 months and 18.1 months, respectively; ORR among patients who had measurable disease at baseline was 23% and 12%, respectively.
Adverse effects associated with the use of Lynparza may include, but are not limited to, the following:
- abdominal pain
- nasopharyngitis/upper respiratory tract infection/influenza
- respiratory tract infection
- decreased appetite
Mechanism of Action
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.