Sapanisertib-based combo beneficial to postmenopausal women with pretreated breast cancer

In postmenopausal women with pretreated everolimus-sensitive or everolimus-resistant breast cancer, use of sapanisertib plus exemestane or fulvestrant is safe and associated with promising clinical activity, according to the results of a phase IB/II trial.

The trial included 118 patients who had previously progressed on everolimus plus exemestane/fulvestrant and received ≤3 (phase IB) or ≤1 (phase II) prior chemotherapy regimens. They were subsequently treated with sapanisertib 3 to 5 mg daily (phase IB; n=24) or 4 mg daily (phase II; n=94) in combination with exemestane 25 mg daily or fulvestrant 500 mg monthly in 28-day cycles.

Researchers enrolled parallel cohorts based on prior response to everolimus in phase II. The goal was to evaluate antitumour activity by clinical benefit rate at 16 weeks (CBR-16).

In phase IB, five patients reported dose-limiting toxicities at sapanisertib doses of 5 mg (n=4) and 4 mg (n=1). The maximum tolerable sapanisertib dose to use in combination with exemestane or fulvestrant was 4 mg daily.

In phase II, CBR-16 was 45 percent in the everolimus-sensitive cohort vs 23 percent in the everolimus-resistant cohort. The respective overall response rates were 8 percent and 2 percent.

Commonly reported adverse events were nausea (52 percent), fatigue (47 percent), diarrhoea (37 percent), and hyperglycaemia (33 percent). Some patients (17 percent) developed rash.

Molecular analysis suggested that patients with AKT1 mutation status were more likely to achieve the best treatment response (complete plus partial response; p=0.0262).