A high response rate to liposomal doxorubicin is seen among women with BRCA mutations treated for recurrent epithelial ovarian cancer

ObjectiveTen percent of ovarian cancer is attributed to hereditary syndromes, most commonly to mutations in the BRCA1 or BRCA2 genes. These cancers are characterized by a prolonged sensitivity to platinum agents in spite of presentation at advanced stages. We hypothesized that women with BRCA-associated ovarian cancer would also show a high response rate to pegylated liposomal doxorubicin (Doxil).MethodsA retrospective cohort study was conducted to compare the response rate, progression-free, and overall survival among women with BRCA-associated or sporadic ovarian cancer who were treated with Doxil.ResultsA response to Doxil was seen in 13 of 23 patients with BRCA mutations (56.5%; 3 by RECIST criteria and 10 by CA125 levels) compared with only 8 of 41 women with non-hereditary cancers (19.5%; 2 by RECIST criteria and 6 by CA125 levels; p = 0.004). This was associated with an improved progression-free and overall survival as measured from the time of Doxil administration. Notably, platinum sensitivity did not directly correlate with a response to Doxil.ConclusionsWomen with BRCA-associated ovarian tumors demonstrate a greater sensitivity to cytotoxic therapy with Doxil than has previously been reported in unselected cases.

► 56.5% of women with BRCA-associated ovarian cancer demonstrated a response to Doxil compared with 19.5% with sporadic disease.
► BRCA mutation carriers had a longer progression-free and overall survival following Doxil treatment.
► The response to Doxil in these cases did not correlate with platinum sensitivity.