MODULE 1: BRCA and Other Potential Genetic Drivers of Ovarian Cancer Development

Key Discussion Topics

• What is the incidence of BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC)? Are there any situations in which a patient diagnosed with EOC should not undergo genetic testing?
• What are some of the similarities and differences between the commercially available genetic testing platforms, and which of these would you recommend for a medical or gynecologic oncologist in community-based practice?
• What is the frequency and clinical significance of somatic BRCA mutations, and what commercially available assays can be used to identify these aberrations?
• What is homologous recombination deficiency (HRD), and how can this phenomenon be identified? Are there any situations in which you are currently attempting to document HRD status?
• Are there any other mutations or genomic abnormalities that may predispose patients to the development of EOC (eg, RAD51C, RAD51D, BRIP1, et cetera)? Is there any evidence demonstrating that one or more of these mutations are sensitive to PARP inhibition?

MODULE 2: Integration of Approved PARP Inhibitors into Ovarian Cancer Treatment Algorithms

Key Discussion Topics

• Do you believe fundamental differences exist among niraparib, olaparib and rucaparib in terms of their mechanisms of action and clinical effectiveness?
• What are the FDA-approved indications for niraparib, olaparib and rucaparib, and how are you currently approaching the use of these agents in your practice?
• How do the toxicities commonly observed with niraparib, olaparib and rucaparib compare in terms of their frequency and severity? Do any of these agents have unique side effects generally not associated with the others?
• In general, are PARP inhibitors more effective in patients with platinum-sensitive disease? Does the type of BRCA mutation (eg, germline versus somatic) have an impact on the efficacy of these agents? Should all patients with OC receive a PARP inhibitor at some point as part of their treatment course?
• What is the biologic rationale for maintenance therapy in OC? How are you currently approaching the use of maintenance therapy for patients with previously treated platinum-sensitive disease? Does your approach change based on response (eg, complete versus partial response) to chemotherapy? Does your approach change based on BRCA status?
• How, if at all, has the recent FDA approval of bevacizumab for platinum-sensitive disease affected your practice?
• What were the design and eligibility requirements for the Phase III NOVA trial evaluating the use of niraparib as maintenance therapy? Which patients ultimately enrolled in NOVA, and how were they stratified?
• What was noted in terms of the absolute improvement in progression-free survival with the use of niraparib compared to placebo in the various study cohorts?
• What were the design and entry criteria for the Phase III SOLO-2 trial evaluating maintenance olaparib? What was reported in terms of efficacy and tolerability? On the basis of these results, do you believe olaparib will eventually be approved as maintenance therapy for patients with BRCA mutation-positive disease?
• From a biologic standpoint, is there any reason to believe that ongoing studies (eg, SOLO-1, PRIMA) evaluating PARP inhibitor maintenance after first-line platinum-based therapy will not be positive and help define the role of these agents in an even earlier disease setting?
• What is known about the use of olaparib in combination with other systemic therapies? Have you used olaparib in combination with other anticancer agents outside of a protocol setting? If so, how?

MODULE 3: Promising Investigational Strategies

Key Discussion Topics

• How, if at all, are the other PARP inhibitors in late-stage clinical development — veliparib and talazoparib — mechanistically different from niraparib, olaparib or rucaparib?
• What clinical research information is available with the use of veliparib? What has been observed in terms of response rates with the use of this agent in patients with BRCA-mutant disease?
• What is known about the efficacy and safety of cediranib as monotherapy and in combination with other agents in the management of OC? Do you believe this drug may one day have a role in this disease?
• What is the incidence of folate receptor alpha positivity in patients with OC, and how is it measured? What is the mechanism of action of the antibody-drug conjugate mirvetuximab soravtansine?
• What has been noted to date in early clinical trials of mirvetuximab soravtansine for individuals with folate receptor alpha-positive OC? Have you seen objective responses in your own practice with the use of this drug? What unique toxicities have been documented with the use of this agent, and how problematic are they to manage?
• How is mirvetuximab soravtansine being evaluated in ongoing Phase III trials, and do you believe it will eventually enter the OC treatment armamentarium?
• What is known about the spectrum of somatic mutations in OC, and which of these appear to be most targetable? How frequently are you ordering next-generation sequencing for patients with OC?
• What is known about the efficacy and safety of immune checkpoint inhibitors in patients with OC?
• What other novel strategies are being investigated in patients with OC? Do any of these look particularly promising?