The US Food and Drug Administration (FDA) has granted full approval to olaparib tablets (Lynparza, AstraZeneca) for use as maintenance therapy for women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have achieved a complete or partial response to platinum-based chemotherapy.
This is not only a new indication for olaparib but also introduces a new formulation of the drug.
Olaparib is the first in a class of drugs that inhibit poly(ADP)-ribose polymerase (PARP). It was initially approved in the United States in 2014 for the treatment of advanced ovarian cancer with BRCA mutations.
That initial approval came as somewhat of a surprise, because earlier that year, the Oncologic Drugs Advisory Committee of the FDA voted against the approval of olaparib.
At that time, olaparib was available in capsules, but the FDA has now approved olaparib tablets for this indication. In their press release, the FDA notes that olaparib tablets and capsules are not interchangeable and that the capsules are currently being phased out of the US market and will only be available through the Lynparza Specialty Pharmacy Network.
Today's approval for maintenance therapy was based on two randomized, placebo-controlled, double-blind, multicenter trials that were conducted in patients with recurrent ovarian cancers who responded to platinum-based therapy.
In the SOLO-2 clinical trial, 295 patients with recurrent germline BRCA-mutated ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned to receive olaparib tablets 300 mg orally twice daily or placebo.
There was a statistically significant improvement in investigator-assessed progression-free survival (PFS) in the olaparib arm as compared to the placebo arm (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.22 - 0.41; P < .0001). The estimated median PFS was 19.1 for olaparib and 5.5 months for placebo.
A blinded independent central review showed an even stronger effect on PFS with olaparib vs placebo: 30.2 months vs 5.5 months.
This represented an improvement of 24.7 months (HR, 0.25; 95% CI, 0.18 - 0.35; P < .0001).
Thus, olaparib reduced the risk for disease progression by 70% to 75% in the study.
"The SOLO-2 data demonstrated a statistically significant and clinically meaningful improvement in outcomes for those who took olaparib," said study author Richard Penson, MD, clinical director of medical gynecologic oncology at Massachusetts General Hospital, Boston, in a statement at the time the results were first presented.
In the second trial, Study 19, 265 patients were randomly assigned to receive olaparib capsules 400 mg orally twice daily or placebo. This cohort differed from that of the SOLO-2 trial in that patients did not have to harbor BRCA mutations.
Results also showed a statistically significant improvement in investigator-assessed PFS in the olaparib arm as compared to placebo (HR, 0.35; 95% CI, 0.25 - 0.49; P < .0001). The estimated median PFS was 8.4 months for the olaparib group and 4.8 months for the placebo group.
The most common adverse reactions (≥20%) in both clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis.
For laboratory abnormalities, the most common (≥25%) were a decrease in hemoglobin, an increase in mean corpuscular volume, a decrease in lymphocytes, a decrease in leukocytes, a decrease in absolute neutrophil count, an increase in serum creatinine, and a decrease in platelets.
The recommended olaparib tablet dose for both maintenance therapy and later-line treatment is 300 mg (two 150-mg tablets) taken orally twice daily with or without food.
The application for this indication was granted fast-track status.
Cite this: FDA Approves New Indication and Formulation for Olaparib - Medscape - Aug 17, 2017.