Ribociclib: Additional Phase III data

Additional data from the double-blind, international Phase III MONALEESA-2 trial in 668 patients with advanced breast cancer showed that median PFS, the primary endpoint, was not reached in patients receiving once-daily 600 mg oral ribociclib for the first 3 weeks of a 4-week cycle plus letrozole vs. 14.7 months for letrozole alone (HR=0.56, p=0.00000329). Additionally, ribociclib plus letrozole led to 12- and 18-month PFS rates of 72.8% and 63%, respectively, vs. 60.9% and 42.2% for letrozole alone. Ribociclib plus letrozole also met the secondary endpoint of improving ORR vs. letrozole alone (40.7% vs. 27.5%, p<0.001). Specifically, ribociclib plus letrozole led to 9 complete responses and 127 partial responses vs. 7 complete responses and 85 partial responses for letrozole alone. In 501 patients with measurable disease at baseline, ribociclib plus letrozole led to an ORR of 52.7%, including 8 complete responses and 127 partial responses, vs. 37.1%, including 6 complete responses and 85 partial responses, for letrozole alone (p=0.00028).

Ribociclib plus letrozole led to >=1 average QTcF interval of >480 msec after baseline in 11 (3.3%) patients vs. 1 (0.3%) patient receiving placebo. The most common grade 3/4 adverse events reported were neutropenia, leukopenia, lymphopenia and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The trial enrolled postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer who received no prior therapy for advanced disease. Data were presented at the European Society for Medical Oncology meeting in Copenhagen and published in The New England Journal of Medicine. Novartis previously reported that the trial was stopped early after a planned interim analysis by an IDMC showed that ribociclib plus letrozole met the primary endpoint of improving PFS vs. letrozole alone (see BioCentury, May 23). ...