Progression-free and Overall Survival Better With Mutations Affecting DNA Repair Genes in Ovarian Cancer

Women with advanced ovarian cancer who had mutations affecting DNA repair genes had longer progression-free and overall survival than women without the mutations, according to a presentation at the Annual Meeting on Women's Cancer.1

These findings come from a phase 3 trial that examined adding bevacizumab to standard chemotherapy in women with advanced ovarian cancer. This analysis examined how mutations in some DNA repair genes affected the response to the combined treatment. The DNA repair genes that were analyzed were ones known as homologous recombination (HR) genes.

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“This is important prognostic information for patients, and highlights the importance of knowing genetic status in clinical trials in ovarian cancer,” said Barbara S. Norquist, MD, a gynecologic oncologist at the University of Washington in Seattle, and lead author of the study.

Norquist and colleagues sequenced DNA from blood, tumors, or both from 1195 women using the sequencing test BROCA-HR, which is a gene panel test.  A total of 307 (25.6%) had a mutation in a gene predicted to affect HR. Of those with mutations, 148 (48.2%) had mutations in BRCA1, 78 (25.4%) in BRCA2, and 81 (26.48%) in one of the other HR genes.

The median progression-free survival was 12.6 months for women with no mutations, 15.7 months for those with BRCA1 mutations, 21.6 months for those with BRCA2 mutations, and 16 months for those with mutations in non-BRCA genes. Median overall survival was 42.1 months for those with no mutations, 55.3 months for those with BRCA1 mutations, 75.2 months for those with BRCA2 mutations, and 56 months for those with mutations in non-BRCA genes.

“All 3 mutation-carrier groups had significantly better progression-free and overall survival when compared to those with no mutations,” Norquist said.

Histology, determined by the appearance of cells viewed with a microscope, was not predictive of mutation status. So, all histologic types of ovarian cancer had these mutations. Only genetic testing, and not histology, was capable of determining mutation status.

“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,” said Norquist. “And if a clinician feels their patient is a candidate for bevacizumab, mutation status does not have a large impact on that decision.”

REFERENCE

1. Norquist BS, Brady MF, Harrell MI, et al. Mutations in homologous recombination genes and response to treatment in GOG 218: an NRG oncology study. Presentation at: 47th Annual Meeting of the Society of Gynecologic Oncology; March 19-22, 2016; San Diego, California.

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