Treatment with Novartis’s BYL719 (alpelisib) was seen to improve progression-free survival (PFS) in the Phase 3 SOLAR-1 clinical trial in patients with HR-positive, HER2-negative advanced breast cancer who received prior treatment with an aromatase inhibitor.
BYL719 is an investigational PI3K inhibitor in development for the treatment of patients with PIK3CA gene mutations.
Approximately 40% of hormone-receptor positive advanced breast cancer patients have mutations in the PIK3CA gene, which provides instructions to make a protein that is involved in the PI3K cell signaling pathway.
Several studies have indicated that PI3K signaling plays a role in several processes that are critical for cancer progression. In fact, activation of the PI3K pathway in breast cancer is associated with a worse prognosis.
Preclinical studies have shown that the use of BYL719 blocks the PI3K pathway.
SOLAR-1 (NCT02437318) is a global, randomized, double-blind, placebo-controlled trial that was designed to evaluate the use of BYL719 in combination with fulvestrant (brand name Faslodex), compared to fulvestrant alone, in patients with HR-positive/HER2-negative PIK3CA-mutated advanced or metastatic breast cancer, who have progressed on or after treatment with an aromatase inhibitor (a class of drugs commonly used in the treatment of breast cancer).
Patients enrolled in the study were randomized in a 1:1 ratio to receive either 300 mg of BYL719 or a placebo, once daily, in combination with 500 mg of fulvestrant intramuscular injections on days 1 and 15 on the first cycle and day 1 of each subsequent 28-day cycle.
The primary endpoint for the study was PFS for patients with the PIK3CA mutation. Secondary endpoints included overall response rate, overall survival, health-related quality of life, clinical benefit rate, efficacy in the PIK3CA non-mutant cohort, tolerability, and safety.
While BYL719 treatment achieved the study’s primary goal — an improvement in progression-free survival — researchers are still assessing data on secondary endpoints.
Concerning safety, the adverse events observed in the study in the BYL719/fulvestrant combination group were generally consistent with those observed in previous BYL719 and fulvestrant studies.
According to Novartis, full results from the study will be submitted to an upcoming medical congress.
“BYL719 is the only alpha-specific PI3K inhibitor and the first one to show potential increased benefit and acceptable tolerability for patients,” Samit Hirawat, MD, head of Novartis oncology global drug development, said in a press release.
“We are encouraged by the results observed in the SOLAR-1 study and look forward to submitting the data to an upcoming medical congress and starting discussions with health authorities worldwide,” Hirawat added.
Currently there are no approved PI3K inhibitors for HR-positive advanced breast cancer. The PI3K pathway is the most frequently altered pathway promoting tumor growth, disease progression, and treatment resistance in HR-positive advanced breast cancer.