Ribociclib Increases Survival in HR+ Advanced Breast Cancer, But…

Lidia Schapira, MD


December 09, 2016

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer

Hortobagyi GN, Stemmer SM, Burris HA, et al
N Engl J Med. 2016;375:1738-1748

Study Summary

Endocrine resistance affects responses and decreases the clinical benefit of antiestrogen therapy for patients with metastatic HR-positive breast cancer. Efforts to overcome resistance using novel drug combinations such as cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors or mTOR inhibitors are underway. In the randomized control trial (RCT) MONALEESA-2, Gabriel Hortobagyi and colleagues explored the combination of ribociclib (Novartis, LEE011) and letrozole as first-line therapy for postmenopausal women with HR-positive breast cancer.

The investigators reported that the phase 3 RCT was conducted at multiple sites between January 2014 and March 2015. A total of 668 postmenopausal women with HR-positive breast cancer were randomly assigned to receive ribociclib + letrozole or letrozole + placebo. The median age was 62. A total of 227 patients had newly diagnosed advanced or metastatic disease, 393 patients had visceral disease, and 147 had bone-only disease.

Progression-free survival (PFS) was significantly longer in the ribociclib group: After 18 months, PFS was 63% in the ribociclib group versus 42% in the placebo group. Grade 3 or 4 adverse events reported in more than 10% of the patients in both groups were limited to neutropenia and leukopenia.

This trial showed improvement in PFS for patients treated with the combination of an aromatase inhibitor plus a CDK4/6 inhibitor, with an increase in reported adverse events constituting myelosuppression.


The results reported here from the MONALEESA-2 trial are similar to those reported previously on the combination of another CDK4/6 inhibitor (palbociclib, Ibrance®) with the antiestrogen fulvestrant in the PALOMA 2 study.[1] In both cases, combination therapy led to improvements in response rates and PFS. We still lack data for long-term health outcomes. Adverse events consisted mostly of asymptomatic myelosuppression in the combination arms.

There are now three leading CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) in clinical trials and all seem to be similar in terms of therapeutic effectiveness. Although these improvements are exciting, we need more research to determine which patients may do well with endocrine therapy alone and which patients will benefit most from combination therapy.



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