Olarigen 150 mg (Olaparib)
Olaparib is indicated as monotherapy for the treatment of adult patients with deleterious or
suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-
negative metastatic breast cancer who have previously been treated with chemotherapy in the neoadjuvant,
adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have
progressed or be considered inappropriate for endocrine therapy. Germline BRCA mutation must be confirmed
before Olaparib treatment is initiated.
Ovarian Cancer: Olaparib is indicated as monotherapy for the maintenance treatment of adult patients with
platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who
are in response (complete response or partial response) to platinum-based chemotherapy.
Pharmacology
Olaparib 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 the 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.
Side Effects
The most common serious adverse reaction reported was anemia (2.4% olaparib vs 2.2% chemotherapy). The
following serious ADRs were reported in one patient each: dermatitis allergy, neutrophil count decreased and
platelet count decreased. The proportion of patients who permanently discontinued Olaparib due to adverse
events was 4.9% in the Olaparib arm compared with 7.7% in the chemotherapy arm. Anemia and platelet count
decrease were the only adverse reactions leading to discontinuation of Olaparib in more than one patient.
