The selective PI3K inhibitor taselisib in combination with fulvestrant has demonstrated efficacy in patients with oestrogen receptor (ER)-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer.

In the randomized, double-blind, placebo-controlled phase III SANDPIPER trial, taselisib in combination with fulvestrant significantly improved investigator-assessed progression-free survival (PFS) among patients with PIK3CA mutation–positive advanced or metastatic breast cancer compared with placebo plus fulvestrant (median, 7.4 months vs 5.4 months; hazard ratio [HR], 0.70; p=0.0037). [Baselga J, ASCO 2018, abstract LBA 1006]

The combination therapy also demonstrated benefits over fulvestrant monotherapy in terms of objective response rate (ORR, 28 percent vs 11.9 percent; p=0,0002), clinical benefit rate (CBR, 51.5 percent vs 37.3 percent), and duration of objective response (DoR, 8.7 months vs 7.2 months). Overall survival (OS) data is still immature.

“This is proof that targeting the PI3K pathway has an effect in breast cancer. About 40 percent of all patients with ER-positive advanced breast cancer have PIK3CA mutations,” said lead investigator Professor José Baselga of the Memorial Sloan Kettering Cancer Center, New York, US.

“The benefit to patients, however, was more modest than we had hoped for, and there are considerable side effects that are associated with the addition of taselisib,” added Baselga.

The most common grade ≥3 adverse events (AEs) among patients who received one or more doses of taselisib plus fulvestrant were diarrhoea (12 percent), hyperglycaemia (10 percent), colitis (3 percent), and stomatitis (2 percent). The AEs led to more discontinuations of the treatment combination (17 percent vs 2 percent) and more dose reductions (37 percent vs 2 percent) as compared with placebo.

“It is encouraging to see a new therapy that can provide some benefits to women with advanced breast cancer. However, because the treatment has side effects, doctors will have to weigh its benefits and risks with their patients,” commented Dr Harold Burstein of the Dana Farber Cancer Institute, Boston, US.

The study enrolled a total of 516 postmenopausal patients with disease recurrence or progression during or after aromatase inhibitor therapy. The patients were randomized to receive oral taselisib 4 mg once daily or placebo in combination with fulvestrant 500 mg. Patients were stratified according to the presence of visceral disease, endocrine sensitivity, geographic region, and presence or absence of PIK3CA mutations.

Based on geographic stratification, the investigators noted that taselisib provided more benefit to study participants from North America and Europe as compared with patients from other countries, including Eastern Europe and Latin America where taselisib appeared to provide very little or no added benefit. Further studies are necessary to understand the reasons for this difference.