Auranofin-sirolimus combo delivers no antineoplastic activity in recurrent ovarian cancer

Inhibition of the protein kinase C iota (PKCι) with auranofin and sirolimus does not provide antineoplastic effects in patients with recurrent high-grade serous ovarian cancer, reports a phase II study.

Twenty-two patients with recurrent high-grade serous ovarian cancer with PKCι expression received auranofin plus sirolimus. Based on unpublished phase I data, dosing consisted of 6-mg auranofin and 5-mg sirolimus orally per day in a 28-day cycle.

Tumour response was the primary endpoint. After the initiation of cancer therapy, the investigators assessed available tumour tissue for PKCι expression using immunohistochemistry and PRKCI copy number via fluorescence in-situ hybridization.

Twenty-one patients were assessable for all clinical trial endpoints. One was excluded for failure to receive a full chemotherapy cycle. All 21 patients showed no tumour response, resulting in early trial termination per a priori trial design.

The median progression-free survival was 2.1 months (95 percent confidence interval [CI], 1.8‒3.7), and the median overall survival was 4.4 months (95 percent CI, 2.6‒12.5).

At least one grade ≥3 adverse event occurred in 14 patients (67 percent). Of the eligible patients, 19 had available tumour tissue, which had a median PKCι copy number averaged per cell of 3. PKCι expression (at least 1+) was found in all trial participants.

“As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ovarian cancer that expressed PKCι,” the investigators said.