All women with ovarian cancer should be offered genetic testing regardless of tumor histology, said Barbara S. Norquist, MD, gynecologic oncologist, University of Washington, Seattle, at the 2016 Society of Gynecologic Oncology meeting. She presented the results of a retrospective, tissue-based analysis of a randomized clinical trial.
Tumors with defects in the HR genes, BRCA1/2 and non-BRCA genes, had as much as a 9-month advantage in progression-free survival (PFS) and a 33-month advantage in overall survival (OS) compared with tumors without HR mutations. The survival advantage appeared across all histologic subtypes, regardless of whether bevacizumab (Avastin) was part of a randomized treatment, Dr Norquist said.
“Mutations affecting homologous recombination were found with all histologic subtypes of ovarian cancer,” said Dr Norquist. “All women with ovarian cancer should be offered genetic testing. Clinical trials that focus on high-grade serous histology are missing a significant fraction of homologous recombination-deficient carcinomas.”
An invited discussant, Kristin K. Zorn, MD, Director, Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, Little Rock, agreed with Dr Norquist’s conclusion about genetic testing. “HR deficiency is common enough in epithelial ovarian cancer that genetic counseling and testing should be offered to all women with this disease.”
However, Dr Zorn added, “It is imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting. Genetic test results can be complex and evolve over time, making genetic counseling and testing a process rather than a one-time event.”
Dr Norquist also reported results from a retrospective analysis of the Gynecologic Oncology Group (GOG) 218 study, a phase 3 randomized clinical trial that showed that adding bevacizumab to paclitaxel and carboplatin significantly improved PFS in patients with advanced primary ovarian cancer. Dr Norquist and colleagues analyzed blood and tissue specimens from 1195 patients who participated in the GOG 218 study to examine the effect of HR gene mutations on response to treatment.
Investigators focused on DNA-damaging mutations in 16 genes predicted to affect the HRgene, including BRCA1/2 and non-BRCA genes. Overall, 148 patients had BRCA1 mutations, 78 patients had BRCA2 mutations, and 81 patients had mutations in other genes. Serous histology accounted for 81% of the specimens, but the frequency of HR-associated mutations did not differ among serous tumors, endometroid tumors, clear-cell tumors, or unspecified carcinomas.
Patients with BRCA2 mutations had a median PFS of 21.6 months, decreasing to 16 months for patients with non-BRCA mutations, 15.7 months with BRCA1 mutations, and 12.6 months for patients whose tumors were mutation free. Having a BRCA2 mutation reduced the risk for disease progression or death by 48%, non-BRCA mutations by 27%, and BRCA1mutations by 20% compared with no mutations.
Patients with no mutations had a median OS of 42.1 months compared with a median OS of 75.2 months with BRCA2 mutations, 55.3 months for BRCA1 mutations, and 56 months for tumors with non-BRCA mutations.
“This is important information for patients, and the findings also suggest that mutation status should be incorporated into clinical trial design,” said Dr Norquist.
