Fulvestrant–sapanisertib combo shows modest benefit in advanced, metastatic breast cancer

Treatment with the combination of fulvestrant plus sapanisertib yields a numerical increase in progression-free survival (PFS) in patients with ER-positive, HER2-negative advanced or metastatic breast cancer as compared with the use of fulvestrant alone, according to the results of a phase II trial. However, the combination is associated with increased toxicity.

The study included 141 postmenopausal women (median age 58 years) with ER-positive, HER2-negative advanced or metastatic breast cancer who progressed during or after aromatase inhibitor treatment. They were randomized to receive fulvestrant 500 mg (28-day treatment cycles) alone (n=46) or in combination with sapanisertib 4 mg daily (n=47) or sapanisertib 30 mg weekly (n=48). Treatment was given until progressive disease, unacceptable toxicity, consent withdrawal, or study completion.

In the overall population, 84.4 percent of patients had demonstrated sensitivity to prior endocrine therapy and 34.0 percent had received prior treatment with CDK4/6 inhibitors. Two-thirds (64.5 percent) of patients exhibited visceral metastases.

Compared with fulvestrant alone, the addition of either daily or weekly sapanisertib dosing prolonged the primary endpoint of median PFS (7.2 and 5.6 months vs 3.5 months, respectively; hazard ratio [HR], 0.77, 95 percent confidence interval [CI], 0.47–1.26 and HR, 0.88, 95 percent CI, 0.53–1.45).

The greatest PFS benefit was observed among patients who had previously received CDK4/6 inhibitors.

In terms of safety, adverse events (AEs) occurred with a greater frequency in the combination group. The most common AEs were nausea, vomiting, and hyperglycaemia. Furthermore, AEs that led to treatment discontinuation were more frequently reported in the two combination therapy groups than in the fulvestrant monotherapy group (32 percent and 36 percent vs 4 percent, respectively).

The findings do not support a favourable risk–benefit profile for the combination of fulvestrant plus sapanisertib in the overall study population.