Updates to MONALEESA-2 Data in HR+ MBC


Important takeaways from MONALEESA-2 trial updates on overall survival data corresponding with the use of ribociclib plus letrozole, as presented at ESMO 2021.

Gabriel N. Hortobagyi, MD, FACP: The MONALEESA-2 randomized phase 3 trial was a clinical trial that initiated in January 2013 and completed accruing in March 2014. We reported the first progression-free survival data, which was the primary efficacy variable at the ESMO [European Society for Medical Oncology Congress] presidential session in 2016 showing highly significant prolongation in progression-free survival for the combination of ribociclib and letrozole compared with the letrozole plus placebo. Five years later, and earlier this year—actually, last month—I presented the overall survival results of the same clinical trial, which had close to 670 patients randomized to the letrozole plus placebo or letrozole plus ribociclib. The overall survival data are equally impressive with a 1-year prolongation of overall survival, with a median overall survival of 51 months for the placebo-plus-letrozole group and 64 months for the ribociclib-and-letrozole group. This represents about a 24% reduction in mortality events, which is a highly significant and highly relevant outcome.

This advantage in overall survival was accomplished with no change in the safety profile we reported 5 years ago, with some symptoms related to fatigue and some laboratory abnormalities, including myelosuppression and reversible liver function abnormalities and more rarely some other reversible safety events. After 6½ years of median follow-up, there have been no new safety signals, there has been no cumulative toxicity, and there have been no treatment-related deaths in this clinical trial.

The clinical implications of the MONALEESA-2 trial are several. No. 1, to date it is the only clinical trial that focuses on postmenopausal women with the metastatic hormone receptor–positive HER2 [human epidermal growth factor receptor 2]–negative breast cancer who haven’t received prior treatment for advanced disease. With the results presented and with the impressive prolongation in overall survival, it makes this combination of ribociclib and letrozole the preferred treatment for this group of patients. We’re awaiting the results of more phase 3 trials with the other CDK4/6 inhibitors in this space, but until similar or competing data becomes available they should be the preferred regimen in this group of patients.

The second implication of these results is that for the first time we’ve crossed a 5-year barrier in terms of median survival for any type of metastatic breast cancer. When I started oncology some 40 years ago, the median survival of patients with metastatic breast cancer was about 2 years. Today the hormone receptor–positive HER2- metastatic breast cancer group, as shown in the MONALEESA-2 trial, is in excess of 5 years. We’ve made significant progress, and this has resulted in an important benefit for our patients. Furthermore, the MONALEESA-2 trial has also shown that this benefit was accomplished without serious toxicity and with the maintenance of the quality of life and, in some cases, improvement of quality of life for those patients who started not with symptomatic disease. All in all, this has been an important step forward in the management of this group of patients.

Transcript edited for clarity.

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