Opening a new chapter in the use of genomic science to fight cancer, the Food & Drug Administration on Friday approved olaparib, a medication for advanced ovarian cancer associated with a defective BRCA gene.
The new drug, to be marketed under the commercial name Lynparza, was found in a preliminary clinical trial to shrink or eliminate ovarian tumors in women whose cancers bore a specific genetic fingerprint and who had undergone at least three prior lines of chemotherapy.
Based on Lynparza's "existing objective response rate and duration of response data," the drug safety agency granted the medication's maker, Astra-Zeneca, an "accelerated" approval. Roughly a third of women with the genetic mutation targeted by Lynparza saw partial shrinkage or complete disappearance of their ovarian tumors over an average of eight months.
At the same time, the FDA granted marketing approval for a "companion diagnostic" that will help identify women whose advanced ovarian cancer is likely to respond to the drug. That test, BRACAnalysis CDx, is made by Myriad Genetics Inc. To be a candidate for Lynparza, a patient must take the test and show positive for a specific mutation of the BRCA gene, which confers a high risk of both breast and ovarian cancer.
"Today's approval constitutes the first of a new class of drugs for treating ovarian cancer," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in the news release.
Pazdur called Lynparza "an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment."
Lynparza is the first of a new class of drugs called poly ADP-ribose polymerase (PARP) inhibitors, which work by blocking the action of an enzyme that helps repair DNA. In certain tumor cells, such as those seen in BRCA1 and BRCA2 mutation carriers, blocking this enzyme can lead to cell death.
"It’s really opening a whole new avenue of therapy," said Dr. M. William Audeh, a medical oncologist and geneticist at Cedars-Sinai Medical Center's Samuel Oschin Cancer Institute in Los Angeles. "This drug is working in a fundamentally different way than chemotherapy: This is a cancer treatment that’s been designed to hit this kind of inherited genetic weakness in the cancer itself."
Because PARP inhibitors such as Lynparza target a cancer's genetic Achilles' heel, they appear to hold out the particular promise of driving some patients' cancer into remission entirely, said Audeh, an investigator on the Astra-Zeneca-sponsored trial assessed by the FDA.
"All of us who’ve done these trials over seven years have some patients who’ve been in long-term remission. That’s not something you see very often with chemotherapy," he added.
Audeh said at least seven other PARP inhibitors are in development and testing for cancers associated with BRCA gene mutations, and for others that may stem from similar mutations.
The arrival of a promising new approach to treating ovarian cancer comes not a moment too soon. Ovarian cancer is rarely detected before it reaches an advanced stage. Some 22,000 women are diagnosed each year with ovarian cancer, and the FDA estimates that 10% to 15% are associated with BRCA gene mutations.
Common side effects of Lynparza were nausea, fatigue, vomiting, diarrhea, headache, decreased appetite, joint and muscle pain, and cold-like symptoms. The FDA noted more serious side effects as well, included lung inflammation; the bone marrow cancer acute myeloid leukemia; and myelodysplastic syndrome, a condition in which the bone marrow is unable to produce enough functioning blood cells.