During a presentation at the European Society for Medical Oncology (ESMO) Congress 2021, results of the phase III MONALEESA-2 study were presented, which evaluated ribociclib in combination with letrozole compared to placebo plus letrozole in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer with no prior systemic treatment for advanced disease. Ribociclib is marketed by Novartis under the commercial name Kisqali®. The results are very promising: ribociclib improved median overall survival (OS) by more than a year, improving OS from 38,9 month to 50,6 months. According to Novartis, this is the longest ever OS reported in HR+/HER2- advanced breast cancer.
Ribociclib in combination with letrozole met its key secondary endpoint of OS, demonstrating a statistically significant and clinically meaningful improvement in survival (median 63.9 vs. 51.4 months; HR=0.76; 95% CI: 0.63-0.93; p=0.004)2. The analysis found that after a median follow-up of over six and a half years, the longest for any CDK4/6 inhibitor trial to date, the improvement in the median OS was over one year2. MONALEESA-2 showed that after five years, patients treated with ribociclib in combination with letrozole had more than a 50% chance of survival (52.3% vs. 43.9%; 95% CI: 46.5-57.7 vs. 38.3-49.4)2.
In MONALEESA-2, a 12-month delay in time to chemotherapy was observed with ribociclib (median 50.6 vs. 38.9 months; HR=0.74; 95% CI: 0.61-0.91) compared to those taking letrozole alone2. With this longer follow-up, no new safety signals were observed; adverse events were consistent with previously reported Phase III trial results for ribociclib.
The primary endpoint progression-free survival (PFS) was met at the initial analysis [median PFS; 95% CI (19.3 months – not reached) vs. 14.7 months (13.0 – 16.5 months); HR=0.556; p=0.00000329]5. These new OS results mark the third statistically significant and clinically meaningful survival benefit achieved by ribociclib in the MONALEESA program.
Ribociclib is approved by the US Food and Drug Administration (FDA) and by the European Commission (EC) as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor. Ribociclib in combination with an aromatase inhibitor is 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 and by the EC9.
Meanwhile, Novartis is now conducting additional cancer trials with ribociclib. The NATALEE study is a large confirmatory clinical trial of ribociclib with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer. And the HARMONIA clinical trial evaluates ribociclib compared to palbociclib in patients with HR+/HER2- advanced breast cancer with aggressive tumor biology, defined as HER2-enriched1.