Novartis Kisqali® data demonstrate superior benefit across main intrinsic subtypes in metastatic breast cancer

IndustryPRwire -- Novartis announced new Kisqali® (ribociclib) data demonstrating consistent efficacy benefit with Kisqali plus endocrine therapy across the main intrinsic subtypes of hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer. The largest biomarker analysis of efficacy in intrinsic subtypes evaluated whether there was a correlation between these subtypes and efficacy outcomes in patients treated with Kisqali across the three Phase III MONALEESA trials. The findings will be presented in an oral presentation at the 2020 San Antonio Breast Cancer Virtual Symposium.

This broad ad hoc exploratory analysis showed that Kisqali plus endocrine therapy consistently provided significant progression-free survival (PFS) benefit across three of four subtypes of HR+/HER2- metastatic breast cancer (LumA HR=0.63; p<.001, LumB HR=0.52; p<.001, HER2-enriched HR=0.39; p<.001, Basal-like HR=1.15; p=.7672). The largest PFS benefit was seen in patients with the HER2-enriched subtype – a non-luminal subtype associated with endocrine resistance and poor prognosis. In contrast, benefit was not observed with palbociclib in the HER2-enriched subtype in a retrospective analysis of the PALOMA-2 trial presented at the 2017 San Antonio Breast Cancer Symposium.

Aleix Prat, Head, Department of Medical Oncology, Hospital Clinic, Barcelona, Spain Commented “The significant benefit seen with ribociclib in the endocrine-resistant HER2-enriched subtype is a unique and important finding, differentiating it from the other CDK4/6 inhibitors. The underlying hypothesis is that ribociclib induces hormone-sensitivity in this group of tumors beyond inhibition of the cell-cycle, The body of preclinical data showing that ribociclib has the ability to more selectively target and inhibit CDK4, which is a key driver of disease progression in breast cancer, may help us understand why ribociclib provides consistent benefit, especially in patients with more aggressive disease.”

The four intrinsic subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched and basal-like) have revealed critical differences in terms of incidence, survival and response to treatment. Additionally, the insights provided by intrinsic subtypes complement and expand upon the information provided by standard clinical parameters and pathological markers. The observed benefit with Kisqali provides reassurance about it as a treatment choice for the majority of people with metastatic breast cancer without the need for additional testing.

Preclinical CDK4/6 Study

Additional data to be presented at SABCS include a poster presentation of a preclinical analysis in which cellular models were used to examine the effects of CDK4/6 inhibitors on either CDK4 or CDK6. The preclinical in vivo study confirmed previously published biochemical in vitro and proliferation data, demonstrating that Kisqali selectively inhibits CDK4, whereas palbociclib has similar activity against both CDK4 and CDK6 in cells3. Kisqali inhibited CDK4 at 11-fold and 9-fold lower drug concentrations than CDK6, whereas palbociclib inhibited CDK4 at 2-fold lower drug concentrations than CDK6 in both cell lines.

Susanne Schaffert, PhD, President of Novartis Oncology Commented “The data presented at SABCS show that Kisqali offers a superior benefit for metastatic breast cancer patients, even in those with the HER2-enriched subtype, who face a very poor prognosis. These data build on previous findings showing Kisqali provides a benefit regardless of type of metastases, endocrine partner or menopausal status. The totality of evidence to date gives us incredible confidence that Kisqali is unique among CDK4/6 inhibitors, and we believe doctors should consider Kisqali for their patients.”

About Kisqali® (ribociclib)

Kisqali is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone. Kisqali is the only CDK4/6 inhibitor to achieve statistically significant OS in two Phase III trials with two distinct patient populations. The substantial OS benefit and improved quality of life observed in MONALEESA-7 support the ESMO Magnitude of Clinical Benefit Scale (MCBS) perfect five out of five rating for Kisqali plus endocrine therapy in premenopausal HR+/HER2- MBC. Kisqali also received an ESMO-MCBS score of four out of five, the highest score achieved by any CDK 4/6 inhibitor in combination with fulvestrant, for first-line postmenopausal patients based on the statistically significant OS benefit observed in MONALEESA-3 and maintained quality of life13. Overall survival follow-up is ongoing for the Phase III MONALEESA-2 trial.

Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali in combination with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide.

Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO).

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

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