FDA approves Lynparza, companion diagnostic for advanced ovarian cancer

The FDA today approved olaparib for heavily pretreated women with advanced ovarian cancer associated with BRCA mutations.

The approval also included a companion diagnostic — BRACAnalysis CDx (Myriad Genetics) — to detect the presence of BRCA mutations in the blood of patients with ovarian cancer who might be candidates for olaparib (Lynparza, AstraZeneca). Ten percent to 15% of ovarian cancers are associated with hereditary defects in BRCA genes, according to the FDA.

“Today’s approval constitutes the first of a new class of drugs for treating ovarian cancer,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “Lynparza is approved for patients with specific abnormalities in the BRCA gene and is an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment.”

Richard Pazdur

The accelerated approval of olaparib — a PARP inhibitor — was based in part on study results from 137 patients with BRCA-mutated ovarian cancer. Overall, 34% of patients responded to treatment, and the mean duration of response was 7.9 months.

The most commonly reported adverse events associated with olaparib included nausea, fatigue, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis, cough, arthralgia, musculoskeletal pain, myalgia, back pain, dermatitis and abdominal pain. Common laboratory abnormalities included increase creatinine; mean corpuscular volume elevation; and decreased hemoglobin, lymphocytes, neutrophils and platelet levels.

Severe adverse events included the development of myelodysplastic syndrome, acute myeloid leukemia and lung inflammation.

In June, the FDA’s Oncologic Drugs Advisory Committee advised against the accelerated approval of olaparib as maintenance therapy in an 11-2 vote; however, the FDA received additional information after the meeting on olaparib’s efficacy in women with ovarian cancer who received at least three prior chemotherapy regimens.

The BRACAnalysis CDx was approved as a laboratory-developed test based on results from the olaparib study. Patients were enrolled on the trial according to the presence of BRCA mutations detected by the companion diagnostic.

“The approval of safe and effective companion diagnostic tests and drugs continue to be important developments in oncology,” Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in the release. “We are very excited that the BRACAnalysis CDx is the FDA’s first approval of a [laboratory-developed test] under a premarket approval application and is the first approval of a [laboratory-developed test] companion diagnostic. The use of companion diagnostics helps bring to market safe and effective treatments specific to a patient’s needs.”