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Novartis phase III trial shows Kisqali combo therapy improves PFS in HR+/HER2- advanced breast cancer

Published 04 June 2018

Novartis has reported 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[1].

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)[1].

"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[1].

"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.

No new safety signals were observed in the MONALEESA-3 trial; adverse events were generally consistent with those observed in MONALEESA-2[1]. The discontinuation rate due to adverse events was 8.5% for Kisqali plus fulvestrant compared to 4.1% for fulvestrant alone[1]

MONALEESA-3 is a Phase III randomized, double-blind, placebo-controlled study evaluating Kisqali in combination with fulvestrant compared to fulvestrant alone for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer who received no prior or only one line of prior endocrine therapy for advanced disease.

A total of 726 people were randomized in the trial, including first-line patients comprised of 367 women who were treatment-naïve and 345 who had received up to one line of prior endocrine therapy for advanced disease. Patients were randomized (2:1) to receive Kisqali plus fulvestrant or fulvestrant alone. Randomization was stratified by the presence or absence of lung or liver metastases and prior endocrine therapy (first-line versus second-line).

Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6).

These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Source: Company Press Release