A study examining mutations in DNA repair genes in women with advanced ovarian cancer found that the disease remained at bay longer in women with the mutations than without, and that women having cancers with these mutations lived longer.
The original study, a phase III clinical trial (Gynecologic Oncology Group 218), was intended to examine the impact of adding the drug bevacizumab to standard chemotherapy for advanced ovarian cancer. In this new study researchers sought to determine whether having mutations in some DNA repair genes (called homologous recombination or HR genes) affected the response to the combined treatment and found that they did not.
More importantly, however, the researchers found that the mutation status affected how long a woman may live (overall survival or OS) and remain free from disease (progression-free survival or PFS).
“This is important prognostic information for patients, and highlights the importance of knowing genetic status in clinical trials in ovarian cancer,” said lead author Barbara S. Norquist, a gynecologic oncologist at the University of Washington in Seattle. She presented the results at the Society of Gynecologic Oncology’s 2016 Annual Meeting on Women’s Cancer March 19 in San Diego.
Dr. Norquist and colleagues sequenced DNA from blood or tumors or both from 1,195 women using the sequencing test BROCA-HR, which is a gene panel test. A total of 307, or 25.6 percent, had a mutation in a gene predicted to affect HR. Of those with mutations 148 (48.2 percent) had mutations in BRCA1, 78 (25.4 percent) in BRCA2, and 81 (26.48%) in one of the other HR genes.
Median PFS and OS for women with no mutations were 12.6 and 42.1 months, respectively. For women with BRCA1 mutations, PFS and OS were longer at 15.7 and 55.3 months. For BRCA2, median PFS and OS were even longer at 21.6 and 75.2 months. And for mutations in non-BRCA genes, median PFS and OS were 16 and 56 months, similar to that seen for BRCA1 mutations.
“All three mutation-carrier groups had significantly better progression-free and overall survival when compared to those with no mutations,” Dr. Norquist said.
Researchers also found that these mutations were present in all histologic types of ovarian cancer (what the cells look like under the microscope).
“This underscores the message that women with any type of ovarian cancer should have genetic testing, and they should be included in clinical trials of drugs that work best in the setting of HR defects. And if a clinician feels their patient is a candidate for bevacizumab, mutation status does not have a large impact on that decision.”