Expanded Approval, New Dosage Form for Olaparib in Recurrent Ovarian Cancer

A new oral dosage form of olaparib (Lynparza), a PARP inhibitor, has been approved as maintenance treatment in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The tablet form has also been approved for women with advanced ovarian cancer who carry defects in the BRCA gene and who have received at least 3 lines of therapy, similar to olaparib capsules, which received accelerated approval in 2014 but are being phased out of the US market.

“Today’s approvals validate more than 10 years of dedicated research behind LYNPARZA, the world’s first PARP inhibitor, which now provides oncologists with the greater flexibility for use in terms of treatment settings. It builds on our recently-announced collaboration with Merck, which aims to further increase the number of treatment options available to patients,” said Sean Bohen, executive vice president, Global Medicines Development and CMO, AstraZeneca, in a statement.

The FDA reviewed results from the phase 3 SOLO-2 trial, which randomized (2:1) patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer to receive olaparib tablets (300 mg) twice daily or placebo. The primary outcome of the study was progression-free survival (PFS); secondary outcomes included overall survival, time to progression, and health-related quality of life, among others.

SOLO-2 met its primary endpoint of investigator-assessed PFS, with olaparib improving the median PFS (19.1 months) by over a year compared with the placebo (5.5 months) (hazard ratio [HR], 0.30; 95% CI, 0.22—0.41; P <.0001). PFS as measured by Blinded Independent Central Review evaluation demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR, 0.25; 95% CI, 0.18—0.35; P <.0001).

The FDA also reviewed results from Study 19, a phase 2 study designed to evaluate the safety and efficacy of olaparib in patients with platinum-sensitive relapsed ovarian cancer. The trial randomized 265 patients, independent of their BRCA status, to receive 400 mg olaparib capsules twice daily or placebo. The estimated median PFS from this trial was 8.4 months, compared with 4.8 months in the placebo group (HR, 0.35; 95% CI, 0.25—0.49; P <.0001).

More than 20% of patients experienced anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, or stomatitis. Common pathologic abnormalities included decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine, and decrease in platelets.