On December 19, 2014, the U. S. Food and Drug Administration approved olaparib capsules (Lynparza, AstraZeneca Pharmaceuticals LP) as monotherapy for the treatment of patients with deleterious or suspected deleterious germline BRCA mutated (gBRCAm) (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Concurrent with this action, FDA approved the BRACAnalysis CDx (Myriad Genetics) for the qualitative detection and classification of variants in the BRCA1 and BRCA2 genes.
The approval is based on objective response rate (ORR) from the international, single-arm trial in patients with deleterious or suspected deleterious gBRCAm advanced cancers. The trial enrolled 137 patients with measurable, gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy.
Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. Of the 137 patients, 93% had ECOG performance status of 0 or 1. Deleterious or suspected deleterious gBRCAm status was verified retrospectively in 97% (59/61) of the patients for whom blood samples were available by the companion diagnostic BRACAnalysis CDx.
The trial results demonstrated an ORR of 34% (95% CI: 26, 42). The median response duration was 7.9 months (95% CI: 5.6, 9.6).
The most common adverse reactions (greater than or equal to 20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.
The recommended olaparib dose is 400 mg orally twice daily.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).