Third Novartis Phase III trial shows Kisqali combination therapy significantly improves PFS in HR+/HER2- advanced breast cancer

Novartis 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 today 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).

“The MONALEESA-3 results in patients treated in this first-line setting were particularly significant. Nearly 70% of women who received ribociclib plus fulvestrant in this setting were estimated to remain progression-free at the median follow-up of 16.5 months,” said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center. “In the advanced breast cancer setting, it is important to ensure we provide patients with treatment options that increase time to disease progression while also maintaining quality of life.”

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.

“MONALEESA-3 data add to the robust body of evidence demonstrating the broad potential of Kisqali to treat pre- and postmenopausal women living with advanced breast cancer in various endocrine combinations and multiple lines of therapy,” said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. “These results along with the other MONALEESA studies build a compelling case that Kisqali combination therapy should be a cornerstone of first-line treatment of HR+/HER2- advanced breast cancer.”

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 (>=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).

Novartis is in discussion with the US Food and Drug Administration (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.

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