Positive results from Phase III SOLAR-1 trial for BYL 719 + fulvestrant in postmenopausal women with PIK3CA mutated hormone-receptor positive, HR+/HER2- metastatic breast cancer. Novartis

Novartis announced positive results from the global Phase III SOLAR-1 trial evaluating the investigational alpha-specific PI3K inhibitor BYL 719 (alpelisib) in combination with fulvestrant. The trial evaluated the efficacy and safety of alpelisib in postmenopausal women with PIK3CA mutated hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer that progressed on or after an aromatase inhibitor with or without a CDK4/6 inhibitor. These data will be presented at the official press briefing at the European Society for Medical Oncology (ESMO) 2018 Congress and as a late-breaker during the Presidential Symposium (Abstract LBA3_PR).

In patients with PIK3CA mutated HR+/HER2- advanced breast cancer, BYL 719 plus fulvestrant demonstrated a median progression-free survival (PFS) of 11 months (95% CI: 7.5-14.5 months) compared to 5.7 months (95% CI: 3.7-7.4 months) for fulvestrant alone. BYL 719 plus fulvestrant reduced the risk of death or progression in those patients by an estimated 35% compared to fulvestrant alone (HR=0.65; 95% CI: 0.50-0.85; p<0.001). overall response rate orr indicating a reduction in tumor size of at least 30 was more than doubled in patients with measurable disease who received byl 719 plus fulvestrant 36 compared to those receiving fulvestrant alone 16. pfs treatment effect was consistent across all subgroups and regardless of whether aromatase inhibitor treatment was given with or without a cdk4 6 inhibitor. the significant pfs improvement demonstrated with byl 719 plus fulvestrant in patients with a pik3ca mutation was not observed for patients without the mutation .most adverse events were mild to moderate in severity and generally manageable through dose modifications and medical management.>

The discontinuation rate of BYL 719 plus fulvestrant due to adverse events was 5% compared to 1% for fulvestrant alone. The most common all-grade adverse events (>=30%) were hyperglycemia (64% vs 10%), diarrhea (58% vs. 16%), nausea (45% vs. 22%), decreased appetite (36% vs. 11%) and rash (36% vs. 6%). Of these, the most common grade 3/4 events (>=5%) were hyperglycemia (37% vs. <1%), rash 10 vs.><1%), and diarrhea 7 vs.><1%).the solar-1 trial is ongoing to evaluate secondary endpoints including overall survival. further analysis from solar-1 will be presented and discussed at future medical congresses.>