Oncofocus Test Kit
includes suggestions for Olaparib
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Lynparza (olaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor. It selectively binds to and inhibits PARP, inhibiting PARP-mediated repair of single strand DNA breaks; PARP inhibition enhances the cytotoxicity of DNA-damaging agents and reverses tumor cell chemoresistance and radioresistance.
Lynparza is specifically indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
Lynparza is supplied as capsules for oral administration. The recommended dose is 400 mg taken twice daily. Continue treatment until disease progression or unacceptable toxicity.
Lynparza was approved for ovarian cancer under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The FDA approval of Lynparza was based on a single-arm study in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced cancers. A total of 137 patients with measurable, gBRCAm associated ovarian cancer treated with three or more prior lines of chemotherapy were enrolled. All patients received Lynparza at a dose of 400 mg twice daily as monotherapy until disease progression or intolerable toxicity. Objective response rate (ORR) and duration of response (DOR) were assessed by the investigator according to RECIST v1.1. The percentage of patients with ORR was 34% and the median DOR was 7.9 months. The percentage with Complete Response was 2% and partial response was 32%.
Adverse effects associated with the use of Lynparza may include, but are not limited to, the following:
- fatigue (including asthenia)
- decreased appetite
- arthralgia/musculoskeletal pain
- back pain
- abdominal pain/discomfort
Myelodysplastic syndrome/Acute Myeloid Leukemia: (MDS/AML) occurred in patients exposed to Lynparza, and some cases were fatal.
Monitor patients for hematological toxicity at baseline and monthly thereafter.
MECHANISM OF ACTION
Lynparza (olaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor. 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.