Positive results from MONALEESA-3 trial of Kisqali plus fulvestrant in advanced or metastatic breast cancer.- Novartis.

Novartis has announced positive results from the third Phase III trial of Kisqali (ribociclib) in advanced or metastatic breast cancer. MONALEESA-3 showed Kisqali plus fulvestrant significantly prolonged progression-free survival (PFS) compared to fulvestrant alone in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer. MONALEESA-3 is the largest phase III trial to evaluate efficacy and safety of a CDK4/6 inhibitor plus fulvestrant in multiple advanced breast cancer patient populations - first-line and second-line settings. These data will be presented as an oral presentation at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract #1000) and published simultaneously in the Journal of Clinical Oncology.

Kisqali in combination with fulvestrant demonstrated a median PFS of 20.5 months (95% CI: 18.5-23.5 months) compared to 12.8 months (95% CI: 10.9-16.3 months) for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732; p=.00000041) across both treatment arms. The median PFS for the subgroup of patients receiving Kisqali plus fulvestrant in the first-line setting, including only de novo patients and those whose disease relapsed >12 months since end of neo(adjuvant) endocrine therapy, was not reached compared to 18.3 months for fulvestrant alone (HR=0.577; 95% CI: 0.415-0.802). In patients receiving treatment in the second-line setting, or those who relapsed <12 months since end of neo(adjuvant) endocrine therapy, the median PFS was 14.6 months compared to 9.1 months for fulvestrant alone (HR=0.565; 95% CI: 0.428-0.744). Fifty percent of the women in MONALEESA-3 had lung and/or liver metastases and showed a consistent treatment benefit compared with the overall population. Follow-up to measure overall survival is ongoing as these data remain immature.

No new safety signals were observed in the MONALEESA-3 trial; adverse events were generally consistent with those observed in MONALEESA-2. The discontinuation rate due to adverse events was 8.5% for Kisqali plus fulvestrant compared to 4.1% for fulvestrant alone. The most common ( greater than = 5%) grade 3/4 adverse events in patients receiving Kisqali plus fulvestrant compared to fulvestrant alone were neutropenia (53.4% vs 0%) and leukopenia (14.1% vs 0%).

Additional Kisqali data are being presented at the 2018 ASCO Annual Meeting. Further results from MONALEESA-7 showed consistent treatment benefit among premenopausal women with HR+/HER2- advanced breast cancer regardless of prior chemotherapy treatment in the advanced setting (Abstract #1047). Initial safety data from the CompLEEment-1 trial demonstrated a consistent safety profile for Kisqali in a patient population more reflective of those seen in a real-world setting (Abstract #1056). Lastly, biomarker data from MONALEESA-2 showed that clinical benefit of Kisqali was consistent across gene expression subgroups with a trend toward greater Kisqali benefit in the high versus low ESR1 expression and low versus high RTK expression subgroups (Abstract #1022).

Comment: Novartis is in discussion with the FDA with respect to a supplemental New Drug Application (sNDA), seeking approval of Kisqali plus fulvestrant for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer.