If homologous recombination deficiency is present in 25% to 50% of our patient population, we’re obviously going to have to factor that into clinical trial design to accurately determine the impact of our experimental therapy.
—Kristin Zorn, MD
Kristin Zorn, MD, Associate Professor and Director of Gynecologic Oncology at the University of Arkansas for Medical Sciences, Little Rock, said that the study’s data confirm the importance of other homologous recombination genes in these defects, not just BRCA1 and BRCA2. “I think this really underscores the NCCN [National Comprehensive Cancer Network] Guidelines for germline testing that have been in place since 2011,” said Dr. Zorn. “All women with a personal history of epithelial ovarian, fallopian tube, or primary peritoneal cancer should be offered genetic counseling and testing.”
According to Dr. Zorn, this recommendation is not dependent on having a family history of cancer, having Ashkenazi Jewish ancestry, or having serous histology. Genetic testing in this population is also particularly important, she revealed, given the availability of drugs that are targeted toward homologous recombination deficiency. Moreover, homologous recombination deficiency increases sensitivity not just to PARP [poly ADP ribose polymerase] inhibitors but to other chemotherapeutic agents, too.
“[Increased sensitivity] has been documented for platinum agents as well as pegylated liposomal doxorubicin and antiangiogenic agents,” she reported, “and this is confirmed again with the data presented here: Women who have defects in these pathways end up having a better overall response to treatment.”
Kristin Zorn, MD
However, as Dr. Zorn reported, patients with homologous recombination deficiency, other than germline BRCA1 and BRCA2 mutations, are not eligible for PARP inhibitor therapy outside of clinical trials.
Key Component of Trial Design
“What I think this is really amounting to is a change in the standard of care for ovarian cancer,” said Dr. Zorn, who added that understanding homologous recombination deficiency is essential to ovarian cancer trial design.
“Limiting enrollment to serous cancer patients potentially excludes many patients who would benefit [from drugs that are active in homologous recombination deficiency tumors]…. In addition, the treatment arms must be balanced for homologous recombination deficiency if we are to accurately interpret the results,” she added.
“If homologous recombination deficiency is present in 25% to 50% of our patient population, we’re obviously going to have to factor that into clinical trial design to accurately determine the impact of our experimental therapy,” Dr. Zorn concluded. ■
Disclosure: Dr. Zorn reported no potential conflicts of interest.