ADAMTS Mutations Predicted Ovarian Cancer Survival, Chemosensitivity

Women with ovarian cancer with ADAMTS mutations were significantly more sensitive to chemotherapy and had longer platinum-free durations compared with women with ADAMTS wild-type tumors, according to the results of a study published recently in JAMA Oncology.

In addition, researchers led by Yuexin Liu, PhD, of the department of pathology at the University of Texas MD Anderson Cancer Center, found that ADAMTS mutations were predictive of improved overall and progression-free survival regardless of BRCA1/2 mutations, stage, residual tumor, and age.

“The early identification of patients who are (or are not) benefiting from platinum-based therapy is central to advancing ovarian cancer management and represents an important step toward the goal of personalized treatment,” the researchers wrote, adding that these results have “important implications for clinical prediction and trial design and may be a useful addition to BRCA mutation assessment for patients with ovarian cancer.”

According to the study, BRCA1 and BRCA2 mutations are found in about 20% of Cancer Genome Atlas patients with ovarian cancer, but chemosensitivity rates to platinum-based therapies are about 70%, meaning that something other than BRCA mutations predict chemotherapy response.

To explore novel genetic mutations that may be associated with chemosensitivity, Liu and colleagues conducted an observational study using genomic and clinical data taken from 512 women with ovarian cancer with available whole-exome sequencing data in the Cancer Genome Atlas project between 2009 and 2014.

Data revealed an approximate 10.4% overall mutation rate for mutations from eight members of the ADAMTS family. These mutations were associated with a significantly higher chemotherapy sensitivity (100% for ADAMTS mutated vs 64% for wild type; P < .001) and a longer platinum-free duration (median duration of 21.7 vs 10.1 months; P = .001).

The researchers also found that those patients with ADAMTS mutations had a significantly longer overall survival (58 vs 41.3 months; hazard ratio [HR] = 0.54; 95% CI, 0.42–0.89; P = .01) and progression-free survival (31.8 vs 15.3 months; HR = 0.42; 95% CI, 0.38–0.70; P < .001) compared with patients with ADAMTS wild type.

Even after adjustment for BRCA mutations, surgical stage, residual tumor, and patient age, patients with ADAMTS mutations had a significantly improved overall survival (P = .01), progression-free survival (P < .001), and platinum-free survival (P = .001).

No significant correlation was found between ADAMTS and BRCA1 or BRCA2 mutations.

“Additional predictors of sensitivity remain to be detected because many patients without ADAMTS or BRCA1 or BRCA2 mutations are chemosensitive,” the researchers noted.