Lynparza tablets (olaparib) tablets were granted FDA approval as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy.
The approval was based on data from the phase 3 SOLO2 trial and the phase 2 study 19 trial. In SOLO2, maintenance treatment with Lynparza showed a 70 percent reduction in the risk of progression or death compared with placebo for patients with platinum-sensitive, relapsed, BRCA-mutant ovarian cancer. In Study 19, the risk of progression or death was reduced by 65 percent with Lynparza versus placebo, regardless of BRCA status.
The FDA noted that the Lynparza tablets and capsules were not interchangeable, and that the capsules were being phased out of the US market. According to the FDA Lynparza capsules will now only be available through the Lynparza Specialty Pharmacy Network. The capsule formulation of Lynparza was approved in 2014 for the treatment of women with BRCA-positive advanced ovarian cancer following treatment with three or more prior lines of chemotherapy.
Eligible patients for the phase 3 SOLO2 trial had relapsed ovarian cancer, confirmed BRCA1/2 mutation, and were in response to their most recent platinum-containing regimen following two or more prior systemic regimens. Investigators in the multicenter international trial randomized patients 2:1 to Lynparza (300-mg tablet twice daily) or to matching placebo. Treatment continued until disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS). The trial protocol included a sensitivity analysis of PFS, performed by a blinded independent central review committee. Secondary endpoints included second PFS (PFS2), overall survival, and safety and tolerability.
Data analysis included 294 randomized patients who received the assigned study treatment. Baseline characteristics did not differ substantively between treatment groups, as 53 percent to 54 percent of patients in each group had attained a partial remission at enrollment; 40 percent of each group had a platinum-free interval of 6 to 12 months; and about 40 percent of patients had received 3 or more prior lines of therapy.
Patients randomized to Lynparza had a median investigator-assessed PFS of 19.1 months compared with 5.5 months in the placebo arm. A prespecified analysis of PFS by a blinded central review committee showed a median PFS of 30.2 months for the Lynparza group versus 5.5 months for placebo, a 75 percent reduction in the hazard for progression and death.
Study 19 assessed patients with platinum-sensitive, recurrent high-grade serous ovarian cancer (265 patients). They had received two or more prior regimens of platinum-based chemotherapy and experienced complete response or partial response to their most recent regimen. In a double-blind, one to one randomization, half the patients received Lynparza 400 mg capsules twice daily as maintenance therapy (136 patients) and half received placebo capsules twice daily (129 patients).
In Study 19, the median PFS for patients taking maintenance Lynparza was 8.4 months, compared to 4.8 months for the control group. The difference in the BRCA mutation subgroup was even more pronounced: 11.2 months with Lynparza and 4.3 months with placebo.
The third data analysis of Study 19, with data cutoff at September 30, 2015, was performed with data at 77 percent maturity, OS in the overall study population (265 patients) was a median 29.8 months in the Lynparza group and 27.8 months in the placebo group. In the BRCA mutation group (n = 136), where the data were at 70 percent maturity, median OS was 34.9 months for the Lynparza group and 30.2 months for placebo.
The most common adverse reactions (more than 20 percent) across studies were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis. The most common laboratory abnormalities (25 percent or higher) were 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.