The PI3K inhibitor taselisib offered less dramatic clinical benefits than anticipated, and with significant toxicities.
Adding the PI3K inhibitor taselisib to standard fulvestrant hormone therapy delayed progression in advanced estrogen receptor (ER)-positive breast cancer by only 2 months compared with fulvestrant alone, and did so at the cost of significant toxicities, according to results of the phase III SANDPIPER trial.
The findings were presented (abstract LBA1006) at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
“Targeting this pathway in breast cancer is effective,” said JosÃ© Baselga, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “However, the benefit to patients was more modest than we had hoped, and there is a risk of considerable side effects.”
Taselisib is a first-in-class agent that blocks the mutated PI3KÎ± protein, the product of a common mutation of the PIK3CA gene. PI3KÎ± hastens tumor invasion of adjacent tissues and metastasis. Approximately 40% of patients with advanced ER-positive breast cancer have PIK3CA mutations.
The study authors enrolled 516 postmenopausal women with locally advanced or metastatic ER-positive, HER2-negative breast cancer refractory to aromatase inhibitor therapy. Patients were randomly assigned to receive standard fulvestrant plus either placebo (n = 176) or taselisib (n = 340).
The most frequent grade 3 or higher adverse events among women receiving taselisib were diarrhea (12%), hyperglycemia (10%), colitis (3%), and stomatitis (2%). Seventeen percent of the women discontinued the study drug due to toxicities, compared with 2% of placebo patients.
“This safety profile is largely consistent with previous studies,” Baselga said.
Women in the taselisib study group experienced a 30% lower risk of tumor progression overall, and taselisib was associated with a 2-month delay in tumor progression (7.4 months vs 5.4 months for placebo; hazard ratio [HR], 0.70; P = .0037).
The overall response rate was “more than doubled” with taselisib (28% vs 11.9%), Baselga noted. Overall survival data are not yet available.
Early clinical trials have suggested that taselisib might offer a clinical benefit to patients with some gynecologic and head and neck cancers.
The regimen’s toxicities mean that oncologists must “weigh its benefits and risks with their patients,” cautioned ASCO expert Harold Burstein, MD, PhD, of Dana-Farber Cancer Institute and Brigham & Women’s Hospital in Boston.