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FDA Approves Olaparib for Maintenance Treatment of BRCA-Mutated, Advanced Ovarian Cancer

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On December 19, 2018, the U.S. Food and Drug Administration (FDA) approved olaparib (Lynparza) for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Patients with germline BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer should be selected for therapy based on an FDA-approved companion diagnostic.

SOLO-1

Approval was based on the SOLO-1 trial, a randomized, double-blind, placebo-controlled, multicenter trial that compared the efficacy of olaparib with placebo in patients with BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer following first-line platinum-based chemotherapy. Patients were randomly assigned 2:1 to receive olaparib at 300 mg orally twice daily (n = 260) or placebo (n = 131).

The primary efficacy outcome was investigator-assessed progression-free survival evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1. The trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival for olaparib compared to placebo. The estimated median progression-free survival was not reached in the olaparib arm and was 13.8 months in the placebo arm (hazard ratio [HR] = 0.30, 95% confidence interval [CI] = 0.23–0.41, P < .0001). At the time of the analysis of progression-free survival, overall survival data were not mature.

Most common (≥ 10%) adverse reactions of any grade occurring in patients who received olaparib in SOLO-1 were nausea, fatigue, abdominal pain, vomiting, anemia, diarrhea, upper respiratory tract infection/influenza/nasopharyngitis/bronchitis, constipation, dysgeusia, decreased appetite, dizziness, neutropenia, dyspepsia, dyspnea, urinary tract infection, leukopenia, thrombocytopenia, and stomatitis.

The recommended olaparib dose is 300 mg (two 150-mg tablets) taken orally twice daily, with or without food, for a total daily dose of 600 mg.

View the full prescribing information for olaparib.

BRACAnalysis CDx

FDA also approved the ­­­­BRACAnalysis CDx test to identify patients with germline BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are eligible for olaparib. The effectiveness of the ­­­­BRACAnalysis CDx test was based on the SOLO-1 trial population for whom deleterious or suspected deleterious germline BRCA-mutated status was confirmed with either prospective or retrospective testing with the BRACAnalysis CDx test.

BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein-coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single-nucleotide variants and small insertions and deletions are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. 

The FDA previously approved BRACAnalysis CDx in several other indications, including:

  • As a companion diagnostic to identify patients with metastatic breast cancer who are eligible for second-line treatment with olaparib (January 2018). 
  • As a complementary diagnostic to identify patients with ovarian cancer who are eligible for second-line treatment with olaparib (August 2017). 
  • As a companion diagnostic to identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib (December 2014). 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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