Adding taselisib to Femara (letrozole) increases the measurable response in certain postmenopausal women with early breast cancer, according to a new study. The benefits were also seen in women whose tumors had mutations in the PIK3CA gene, researchers reported in a press release.
The findings were recently presented at the European Society for Medical Oncology (ESMO) 2017 Congress, with the title “Primary results of LORELEI: a phase II randomized, double-blind study of neoadjuvant letrozole (LET) plus taselisib versus LET plus placebo (PLA) in postmenopausal patients (pts) with ER+/HER2-negative early breast cancer (EBC).” They were based on data from the recently completed Phase 2 LORELEI study (NCT02273973).
Taselisib, an PI3K inhibitor developed by Roche, works by blocking a protein called PI3K (short for phosphoinositide 3-kinase), which helps cancer cells grow.
LORELEI, a randomized, double-blind study, was designed to determine whether taselisib could be used to enhance Femara’s effects in postmenopausal women with operable early breast cancer that is estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative.
Participants — 344 in total — were recruited at 90 centers worldwide, and their tumors were analyzed for mutations in PIK3CA.
Patients were randomized to receive Femara in combination with taselisib or placebo in a five-days-on, two-days-off schedule. The schedule was maintained for 16 weeks, after which patients underwent surgery.
The study’s co-primary goals were to determine the percentage of patients who saw their tumors shrink, using MRI scans, and the number who had a pathologic complete response — deemed a complete eradication of the tumor in both the breast and lymph nodes — at date of surgery. These measures were assessed in the entire study population of postmenopausal women with operable early breast cancer and in those with PIK3CA-mutant tumours.
In the overall cohort, adding tesalisib to Femara increased the percentage of patients who responded to the therapy from 39.3 percent to 50 percent.
Similar findings were seen in the patients with PIK3CA-mutated tumors, where the overall response rate improved from 38 percent in the placebo group to 56.2 percent in the tesalisib group.
No significant differences were seen in the amount of patients achieving a pathological complete response in either the overall population or patients with the PIK3CA mutation.
Toxicity linked to taselisib was manageable. The most common grade 3 and 4 adverse events included gastrointestinal disorders, infections and skin disorders, vascular disorders, and metabolism and nutrition disorders, including hyperglycemia.
This is the first time a specific PI3K inhibitor has proven effective in early stage breast cancer, said Nadia Harbeck of the Breast Center, Department of Obstetrics and Gynecology, University of Munich, commenting on the results. Further research is now ongoing to determine which patients are more likely to benefit from the combination.
The team also is waiting for Phase 3 trials that confirm their findings in metastatic breast cancer patients.