BRACAnalysis CDx as a companion diagnostic tool for Lynparza

Abstract

Lynparza and its companion diagnostic test, BRACAnalysis were approved by the US FDA in December 2014 for recurrent ovarian cancer in women with a germline BRCA mutation. Women with a deleterious BRCA mutation are predisposed to ovarian cancer due to deficient homologous recombination repair. Inhibition of the PARP enzyme forces use of an alternate error-prone pathway for repair; PARP trapping is another mechanism utilized that blocks cellular replication by trapping inactivated PARP onto single-stranded DNA breaks. Although many companion diagnostic kits are already in use in oncology, BRACAnaylsis is unique in several ways including comprehensive BRCA gene germline profiling, availability to all women with ovarian cancer and implications for family members.

Keywords:

• BRCA mutation
• companion diagnostic
• hereditary
• Lynparza
• ovarian cancer
• PARP inhibitor

Financial & competing interests disclosure

KN Moore is a member of the advisory boards of Amgen, Astra Zeneca, Genentech, Immunogen and Advaxis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Lynparza along with its companion diagnostic test, BRACAnalysis were FDA approved in December 2014 for use in recurrent ovarian cancer patients with a deleterious BRCA mutation; it was the first therapy to be FDA approved for women with a deleterious BRCA mutation. The provocative results of Study 19, a Phase II trial of maintenance olaparib versus placebo were the impetus for approval.

• PARP inhibitors such as Lynparza have robust activity in women with a BRCA mutation (germline and somatic); their activity in patients without a BRCA mutation but with a deficiency in homologous recombination repair has been proven, and research is ongoing how to safely and efficiently identify these patients.

• BRACAnalysis comprehensively evaluates the BRCA1 and BRCA2 genes to assess for a mutation rather than identifying a point mutation as other companion diagnostic tests do. It utilizes PCR and Sanger sequencing, and it was validated by performance of next generation sequencing with comparable results.

• BRACAnalysis is recommended and available to all women with ovarian cancer to identify those with a BRCA mutation and thus enable proper administration of targeted therapies such as PARP inhibitors.

• BRACAnalysis is relatively affordable, and attempts are being made for all patients to gain access.