The US Food and Drug Administration (FDA) granted approval for the use of olaparib (Lynparza, AstraZeneca) as maintenance therapy for adult patients with recurrent ovarian cancer who have achieved a complete or partial response to platinum-based chemotherapy. The agent is also now approved in tablet form for this and earlier indications.
“Physicians have almost 3 years of clinical experience with Lynparza on the market and we are now pleased to bring this important medicine, in a new tablet formulation, to a broader group of women,” said Sean Bohen, MD, PhD, the chief medical officer of AstraZeneca, in a press release.
Olaparib, a PARP inhibitor, was first approved in December 2014 in its capsule formulation, involving eight capsules twice daily. It was indicated for patients with deleterious or suspected deleterious germline BRCA-mutant advanced ovarian cancer, who had received at least three prior lines of chemotherapy. The new approval of the tablet formulation, involving two tablets twice daily, will replace the capsules in that indication; according to the FDA, the capsules are being phased out in the United States, and will be available only through the Lynparza Specialty Pharmacy Network.
The approval of olaparib for use as maintenance therapy is based on data from two clinical trials of patients who responded to platinum-based therapy. In the SOLO-2 trial, 295 patients were randomized to receive either olaparib tablets (300 mg twice daily) or placebo; all patients in that study had germline BRCA mutations and recurrent ovarian, fallopian tube, or primary peritoneal cancer.
The median progression-free survival (PFS) in SOLO-2 was 19.1 months with olaparib, and 5.5 months with placebo, for a hazard ratio (HR) of 0.30 (95% CI, 0.22–0.41; P < .0001).
The other trial, Study 19, included 265 patients regardless of BRCA mutation status. They were randomized to receive olaparib tablets at a slightly higher dose (400 mg twice daily) or placebo, and again the study drug showed significant improvement in PFS. The median PFS was 8.4 months with olaparib, compared with 4.8 months with placebo, for an HR of 0.35 (95% CI, 0.25–0.49; P < .0001).
The most common adverse effects of olaparib include anemia, nausea, fatigue, vomiting, and others. Laboratory abnormalities occurring in at least 25% of patients in the studies included decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, and others.
“Today’s approval is welcome news for US patients with ovarian cancer, who are now able to benefit from treatment with olaparib irrespective of their BRCA mutation status,” said Eric Pujade-Lauraine, MD, of Université Paris Descartes in France, who was the principal investigator of the SOLO-2 trial.
The approval is specifically for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, and the recommended dose is 300 mg twice daily.