Gene mutations extend PFS, OS in ovarian cancer

Issue: April 25, 2016

The presence of germline and somatic gene mutations significantly prolonged PFS and OS in women with advanced ovarian cancer undergoing treatment with bevacizumab plus standard chemotherapy, according to study results presented at the Society of Gynecologic Oncology 47th Annual Meeting on Women’s Cancer.

Researchers noted gene mutations were present for all histologic types of ovarian cancer. Thus, histology was not predictive of mutation status.

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

Barbara S. Norquist

Norquist and colleagues evaluated data from the Gynecologic Oncology Group (GOG) 218 trial — a phase 3, randomized trial in which researchers assessed the role of bevacizumab (Avastin, Genentech) plus carboplatin and paclitaxel for women with advanced primary ovarian, fallopian tube and peritoneal carcinoma.

For the current analysis, researchers sought to assess whether mutations in homologous recombination genes affected response to treatment. They used the BROCA-HR assay (University of Washington) to sequence germline and somatic DNA from 1,195 women from the GOG 218 trial.

Overall, 307 women (25.6%) harbored a gene thought to affect homologous recombination. Of these 148 (48.2%) had mutations in BRCA1, 78 (25.4%) had mutations in BRCA2 and 81 (26.48%) had mutations in non–BRCA homologous recombination genes.

Histology did not predict mutation status; however, a significantly smaller proportion of patients with low-grade serous carcinoma harbored a mutation than patients with high-grade serous histology (10.9% vs. 27%; OR = 0.33; 95% CI, 0.1-0.8).

Median PFS was longer among women with BRCA1 (15.7 months), BRCA2 (21.6 months) or mutations non-BRCA genes (16 months) than women without mutations (12.6 months).

Further, median OS was 55.3 months among women with BRCA1 mutations, 75.2 months among women with BRCA2 mutations, 56 months among women with a non-BRCA mutation, but 41.1 months among women without a mutation.

After the researchers adjusted for treatment, stage, residual disease and performance status, HRs for progression and death were significantly lower for those with mutations vs. those without mutations. This benefit occurred for women with BRCA1 mutations (HR for PFS = 0.8; 95% CI, 0.66-0.97; HR for OS = 0.74; 95% CI, 0.59-0.94), BRCA2 mutations (HR for PFS = 0.52; 95% CI, 0.40-0.67; HR for OS = 0.36; 95% CI, 0.25-0.53), and non–BRCA homologous recombination mutations (HR for PFS = 0.73; 95% CI, 0.57-0.94; HR for OS = 0.67; 95% CI, 0.49-0.9).

Norquist and colleagues are planning an additional analysis assessing PFS and OS by mutation status and treatment arm.

“All three mutation-carrier groups had significantly better PFS and OS when compared to those with no mutations,” Norquist said in the release. “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 homologous recombination defects. If a clinician feels their patient is a candidate for bevacizumab, mutation status does not have a large impact on that decision.” – by Jennifer Southall

Reference: Norquist BS, et al. Opening Scientific Plenary Session I. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 19-22, 2016; San Diego.

Disclosure: The researchers report no relevant financial disclosures.