Olaparib (Lynparza; AstraZeneca) is an oral PARP inhibitor that provides inhibition of PARP enzymes that interfere with cell cycle and DNA repair. Tumor cells with mutated BRCA1/2 lack an alternative pathway for DNA repair making them sensitive to the effects of PARP inhibition. The pivotal data for approval of olaparib in heavily pretreated gBRCA-mutated ovarian cancer are derived from a phase 2, non-comparative, open-label, and nonrandomized, single-arm study in patients with deleterious or suspected deleterious gBRCA-mutated advanced cancers. This study enrolled 137 patients with measurable, gBRCA-mutated advanced ovarian cancer treated with 3 or more prior lines of chemotherapy. This patient subset was referred to as Study 1 in the FDA approved package insert and comprised the pivotal data on which the drug was approved. 

Lynparza is FDA approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy and for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza
Study 42- Of the 193 patients with ovarian cancer in study 42, 137 patients with measurable, gBRCA-mutated ovarian cancer treated with 3 or more prior lines of chemotherapywere assessed.  Almost all patients has previous platinum-containing therapy and a majority also had received paclitaxel, doxorubicin, and gemcitacbine.  All patients received single-agent, oral olaparib at a dose of 400mg twice daily until disease progression or intolerable toxicity.  Objective response rate (ORR) and duration of response were assessed by the investigators according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. ORR was 34% (95% confidence interval [Cl]. 26-42); there were 2% completed response and 32% partial response.  Median duration of response was 7.9 months (95% Cl, 5.6 to 9.6).  Based on limited data, olaparib has efficacy in patients with heavily (>3 prior lines of chemotherapy) pretreated gBRCA mutation positive ovarian cancer.  The effect of olaparib on survival is unknown.

SOLO-2 (NCT01874353) was a double-blind, placebo-controlled trial in which patients (N=295) with germline BRCA-mutated (gBRCAm) ovarian, fallopian tube, or primary peritoneal cancer were randomized (2:1) to receive Lynparza tablets 300 mg orally twice daily or placebo until unacceptable toxicity or progressive disease.  The major efficacy outcome was investigator-assessed progression-free survival (PFS) evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Additional endpoints included overall survival (OS). SOLO-2 demonstrated a statistically significant improvement in investigator-assessed PFS in patients randomized to Lynparza as compared with placebo. Investigator-assessed median progression-free survival was significantly longer in the olaparib group than in the placebo group (19·1 months [95% CI 16·3–25·7] with olaparib vs 5·5 months [5·2–5·8] with placebo; HR 0·30 [95% CI 0·22–0·41], p<0·0001; figure 2A). According to the Kaplan-Meier survival estimator, 12-month progression-free survival was 65% (95% CI 57·8–71·4) in the olaparib group versus 21% (13·3–29·6) in the placebo group

Approval is for 12 months at 400mg twice daily.