10 Oct Ribociclib and Letrozole May Represent Paradigm Shift in Treating HR+ Advanced Breast Cancer
MedicalResearch.com Interview with:
Gabriel N. Hortobagyi, MD, FACP, F.A.S.C.O.
Professor of Medicine
Nellie B. Connally Chair in Breast Cancer
Department of Breast Oncology
Co-Director, Multidisciplinary Breast Cancer Research Program
University of Texas MD Anderson Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: MONALEESA-2 is a Phase III randomized, double blind, placebo controlled, multicenter global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer.
The primary efficacy results from the pivotal MONALEESA-2 study show LEE011 (ribociclib) plus letrozole significantly extended progression-free survival (PFS) compared to a standard of care, letrozole, as a first-line treatment in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (HR= 0.556; 95% CI: 0.429-0.720; p=0.00000329)1.
The results demonstrate that LEE011 plus letrozole reduced the risk of death or progression by 44% over letrozole alone, significantly extending PFS across all patient subgroups. More than half of women with measurable disease taking LEE011 plus letrozole saw their tumor size shrink by at least 30% during treatment (overall response rate (ORR) in patients with measurable disease = 53% vs 37%, p=0.00028)1.
Most adverse events in the MONALEESA-2 trial were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and/or reduction1.
The discontinuation rate due to adverse events in the MONALEESA-2 trial was 7.5% for LEE011 plus letrozole and 2.1% for letrozole alone1.
The most common grade 3/4 (most severe >5% of patients in either arm, regardless of relationship to study treatment) adverse events were as follows for LEE011 plus letrozole compared to letrozole alone: neutropenia (60% vs 1%), leukopenia (21% vs 1%), elevated alanine aminotransferase (9% vs 1%), lymphopenia (7% vs 1%) and elevated aspartate aminotransferase (6% vs 1%)1.
MedicalResearch.com: What should readers take away from your report?
Response: These findings could represent a paradigm shift in the way we treat HR+ advanced breast cancer. The combination of ribociclib and letrozole was well tolerated and because the magnitude of the difference between the treatment and placebo arms, we were able to declare the primary efficacy endpoint of superior median PFS was met ahead of schedule. This powerful therapeutic effect will prolong progression free survival for women for many months.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: As part of the robust MONALEESA clinical trial program, we are continuing to evaluate the potential benefit of ribociclib in combination with other endocrine therapies and across a broad range of patients.
In MONALEESA-3, we are evaluating ribociclib in combination with fulvestrant compared to fulvestrant alone in men and post-menopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy.
In MONALEESA-7 we are investigating ribociclib in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in pre-menopausal women with HR+/HER2- advanced breast cancer who have not previously received endocrine therapy.
Both Phase III trials, MONALEESA-3 and MONALEESA-7 are fully enrolled.
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Hortobagyi G, Stemmer S, Burris H, et al. First-line ribociclib plus letrozole for postmenopausal women with HR+, HER2-, advanced breast cancer: First results from the Phase III MONALEESA-2 study. Presented at the European Society for Medical Oncology (ESMO) Congress, October 8, 2016, Copenhagen, Denmark (abstract # LBA1_PR)
Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer
Up to 75% of breast cancers express the estrogen receptor or progesterone receptor (hormone-receptor [HR]–positive). Endocrine therapy is the standard of care for postmenopausal women with advanced breast cancer that is HR-positive and human epidermal growth factor receptor 2 (HER2)–negative, with…
October 7, 2016 Hortobagyi G.N., Stemmer S.M., Burris H.A., et al.
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