Additional analysis of phase III SOLAR-1 trial of BYL 719 + fulvestrant PIK3CA mutated HR+/HER2- advanced or metastatic breast cancer.- Novartis

Novartis has announced additional analysis from the global Phase III SOLAR-1 trial investigating the alpha-specific PI3K inhibitor BYL 719 (alpelisib) in combination with fulvestrant in men and postmenopausal women with PIK3CA mutated hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. In SOLAR-1, the addition of BYL 719 to fulvestrant nearly doubled median progression-free survival (PFS) in patients with PIK3CA mutated HR+/HER2- advanced breast cancer who progressed on or after an aromatase inhibitor (AI) compared to fulvestrant alone.

In this analysis, BYL719 plus fulvestrant also showed consistent clinically meaningful treatment benefit after progression on an AI or after receiving up to one additional line of therapy for advanced breast cancer. These data will be presented today during an oral presentation at the 2018 San Antonio Breast Cancer Symposium (SABCS) (Abstract #GS3-08).

Approximately 40% of patients living with HR+ advanced breast cancer have a PIK3CA mutation, which over activates the PI3K pathway. When activated, the PI3K pathway is associated with tumor growth, resistance to endocrine treatment and a poor overall prognosis. Currently there are no approved treatments for breast cancer that specifically target this mutation.

BYL 719 in combination with fulvestrant consistently improved median PFS in patients with PIK3CA mutated HR+/HER2- advanced breast cancer who progressed within 12 months of AI treatment (mPFS: 11.0 months vs 6.8 months for fulvestrant alone) or received up to one additional line of therapy for advanced breast cancer (mPFS: 10.9 months vs 3.7 months, respectively). Most adverse events were mild to moderate in severity and generally manageable through dose interruption, dose reductions and medical management. Treatment discontinuation rate due to adverse events in those with a PIK3CA mutation receiving BYL 719 plus fulvestrant was 3% compared to 2% for fulvestrant alone. The most frequent all-grade adverse events (>=40%) were hyperglycemia (65% vs 9%), diarrhea (54% vs 11%), nausea (46% vs 20%) and rash (40% vs 6%). The most common grade 3/4 events (>=10%) were hyperglycemia (37% vs <1%) and rash (13% vs><1%).>

Mutation status of participants in SOLAR-1 was identified by a clinical trial assay developed by Qiagen . A significant PFS benefit was observed for BYL 719 plus fulvestrant in patients with a PIK3CA mutation regardless of whether the mutation was identified by a tumor tissue test or ctDNA test, suggesting the potential viability of using liquid biopsies to identify PIK3CA mutation status (tissue positive HR=0.65; mPFS 11.0 months; plasma positive HR=0.56; mPFS 10.9 months). Novartis has entered into agreements with both Qiagen and Foundation Medicine to develop flexible companion diagnostic solutions for BYL719 that utilize both tumor tissue and plasma sample types.