New breast cancer treatment approved by USFDA

Olaparib is an approved drug against BRCA-mutated, advanced ovarian, fallopian tube, primary peritoneal and recurrent epithelial ovarian cancer; for complete or partial chemotherapy responsiveness cases. The FDA approval of January 2018, sets an important benchmark for cancer treatment.

The drug is the first and only PARP inhibitor approved for treatment of BRCA mutated, metastatic breast cancer

Olaparib is now approved for the treatment of BRCA-mutated (gBRCA HER2-negative)  metastatic breast cancer. Patient selection for Olaparib treatment, however, must be based on a USFDA-approved genetic test such as BRACAnalysis CDx, a companion diagnostic test developed by Myriad Genetics.

Olaparib is a poly ADP-ribose polymerase (PARP) inhibitor and the first targeted drug therapy against BRCA mutations to selectively kill malignant cells. The cytotoxic drug selectively targets DNA damage response by inhibiting PARP enzymatic activity, increasing PARP-DNA complex formation and leading to DNA damage and the death of malignant cells.

Olaparib, under its trade name Lynparza, has been jointly developed by AstraZeneca, Merck, KuDOS Pharmaceuticals and University of Sheffield scientists, and the drug is being investigated as a treatment for prostate and pancreatic cancers. A randomized, open-label, multi-centric (International) Phase III study (OlympiAD) was conducted to demonstrate the safety and efficacy of Olaparib (300 mg twice daily) in HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations. The treatment results were compared with physician’s choice of chemotherapy. The study enrolled 302 patients across North America, South America, Europe and Asia.

The study participants had HER2-negative gBRCA1- or gBRCA2- mutated breast cancer, which was either HR+ (n=152) or triple negative (n=150). Among the participants, 205 patients who were aged between 22 and 76 were assigned to receive Olaparib. The inclusion criteria allowed participants exposed to the prior treatment of anthracycline and taxane chemotherapy, but no more than two cycles of chemotherapy for metastatic cancer.

Administration of Olaparib significantly improved progression-free survival rate (primary endpoint) by seven months, compared to four and a half months of chemotherapy. Olaparib also improved overall survival rate (secondary endpoint) by delaying the progression of disease in Olaparib-received patients.

Some of the reported common adverse effects of Olaparib treatment were nausea, vomiting, anemia, neutropenia, leukopenia, joint pain, respiratory tract infection, headache, dyspepsia, stomatitis, dysgeusia, and diarrhea. Severe adverse events of Olaparib included the occurrence of acute myeloid leukemia, myelodysplastic syndrome, and pneumonitis.

Clinical trial studies found a possible drug-drug interaction of Olaparib with anti-cancer agents including DNA-damaging agents, which may lead to development or prolongation of myelosuppressive toxicity. It has been recommended that Olaparib is not concomitantly used with moderate or strong CYP3A inhibitors and/or CYP3A inducers. It has also been recommended to discourage patients from consuming Seville oranges, grapefruit or their juices during Olaparib treatment. Until present, there are no listed contraindications for Olaparib treatment.