NEJM publication of Novartis Kisqali Data Shows Longest Median Overall Survival Ever Reported in HR+/HER2- Advanced Breast Cancer

The New England Journal of Medicine (NEJM) published data showing the Phase III MONALEESA-2 trial for NovartIs’s Kisqali (ribociclib) plus letrozole demonstrated a statistically significant improvement in overall survival.

The data show more than a 12 month increase in overall survival for Kisqali plus letrozole compared to letrozole alone, in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. MONALEESA-2 overall survival data were first presented at the European Society for Medical Oncology (ESMO) Congress in September 2021. The NEJM publication includes additional analyses substantiating the longest median overall survival benefit ever reported for HR+/HER2- advanced breast cancer patients, supporting the use of Kisqali combination therapy as a first-line treatment, Novartis explained in its press release.

“These positive MONALEESA-2 overall survival data mark tremendous progress in extending the lives of patients living with advanced breast cancer. Achieving overall survival is the gold standard of clinical trials and is particularly impressive in the first-line setting,” said Gabriel N. Hortobagyi, MD, FACP, Professor of Medicine, University of Texas MD Anderson Cancer Center. “Despite higher subsequent use of CDK4/6 inhibitor therapy in the placebo arm, the ribociclib treatment arm demonstrated a statistically significant overall survival benefit of more than one year. These data solidify ribociclib and letrozole as the preferred CDK4/6 inhibitor combination to offer postmenopausal women with HR+/HER2- advanced disease more time.”

Novartis noted in the press release that NEJM publication includes the following findings:

Median overall survival among patients in the Kisqali plus letrozole group was over five years (63.9 months) compared to four years (51.4 months) for the placebo group (HR=0.76; 95% CI: 0.63-0.93; two-sided p=0.008).
Patients who received Kisqali plus letrozole as first-line therapy saw a 24% reduction in risk of death compared to those receiving letrozole alone.
The overall survival benefit with Kisqali plus letrozole continued to increase over time​, with the survival rate of patients receiving Kisqali plus letrozole at 52.3% at five years (8.4% higher than letrozole alone) and 44.2% at six years (12.2% higher than letrozole alone).
Fewer patients in the Kisqali plus letrozole group received subsequent treatment with any-line CDK4/6 inhibitor therapy (34.4% for letrozole alone compared to 21.7%); the significant overall survival benefit with Kisqali plus letrozole was consistent after adjusting for subsequent treatment with any-line CDK4/6 inhibitors.
Patients on Kisqali plus letrozole compared to those on letrozole alone experienced an additional one-year delay to subsequent chemotherapy (50.6 months compared to 38.9 months in the placebo group).
This study has the longest reported follow-up for any CDK4/6 inhibitor clinical trial to date with a median of 80 months, with no new safety signals emerging; adverse events were consistent with previously reported Phase III trial results for Kisqali.

“What’s most compelling about these MONALEESA-2 data is to see that the overall survival benefit of Kisqali plus letrozole was improving over time for patients, regardless of disease characteristics. These meaningful outcomes are elevating the standard of care for people living with advanced breast cancer, who now have hope for a longer quality life,” said Susanne Schaffert, PhD, President, Novartis Oncology. “Data continue to show that Kisqali sets itself apart from other CDK4/6 inhibitors, and we look forward to continue studying all its potential benefits for patients living with HR+/HER2- breast cancer.”

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

Further sub-analyses from these data will be shared with the scientific community later this year, the company said.