22 Dec First-line ribociclib + letrozole in patients with de novo HR+, HER2- Advanced Breast Cancer
MedicalResearch.com Interview with:
Dr. Joyce O’Shaughnessy
Joyce O’Shaughnessy, MD
Co-Chair, Breast Cancer Research
Texas Oncology-Baylor Charles A. Sammons Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The MONALEESA-2 trial is a Phase III, randomized, double-blind, international study of LEE011 in combination with letrozole vs. letrozole alone, in postmenopausal women with HR+/HER2- advanced breast cancer who had received no prior systemic therapy for advanced disease.
Because de novo disease has not been previously treated with systemic treatment for early-stage breast cancer, tumors may exhibit a different disease biology, which could result in varied responses compared to patients who experience recurrence of their initial breast cancer. We analyzed a pre-defined subgroup of women with de novo HR+/HER2- advanced breast cancer to better understand the response of LEE011 plus letrozole in this patient population.
In the de novo advanced breast cancer patient sub-group, progression free survival was significantly prolonged; LEE011 plus letrozole reduced the risk of disease progression or death by 55% over letrozole alone (HR=0.448 [95% CI: 0.267–0.750]). The 12-month PFS rate was 82% in the LEE011 plus letrozole arm compared to 66% with letrozole alone.
Most adverse events were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The most common all-grade adverse events (≥30% of patients with de novo advanced breast cancer) in the LEE011 plus letrozole arm were neutropenia (70.2%), nausea (48.2%), fatigue (42.1%), alopecia (39.5%), and leukopenia (31.6%).
MedicalResearch.com: What should readers take away from your report?
Response: Results from the de novo subgroup of women in the MONALEESA-2 trial establish ribociclib in combination with letrozole as a meaningful treatment option in the first-line setting for this patient population. These women are often diagnosed initially with advanced breast cancer that has already metastasized, so it is critical to start them with treatments that extend time until disease progression.
In the broader MONALEESA-2 study, treatment benefit was seen across subgroups and regardless of the number of metastatic sites. Should LEE011 receive FDA approval, these subgroup analyses may help oncologists be more confident recommending LEE011 in combination with letrozole as a treatment option because they can better understand which patients are the best candidates based on their individual disease.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: LEE011 is being assessed through the robust MONALEESA clinical trial program, which includes MONALEESA-2, MONALEESA-3, and MONALEESA-7. The MONALEESA-2 study is ongoing to evaluate secondary endpoints, including overall survival. The other MONALEESA trials are evaluating LEE011 in multiple endocrine therapy combinations across a broad range of patients, including men and premenopausal women.
MedicalResearch.com: Is there anything else you would like to add?
Response: LEE011 received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) in August 2016 and Priority Review in October 2016, which may lead to faster access for US patients. EMA has also accepted the marketing authorization application.
Disclosure: Study supported by Novartis
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Last Updated on December 22, 2016 by Marie Benz MD FAAD