The addition of LEE011 (ribociclib) to Femara® (letrozole) significantly improved the survival time without cancer progression compared to letrozole only in advanced, hormone-positive breast cancer. These results were presented at the 2016 annual San Antonio Breast Cancer Symposium (SABCS).
The majority of all breast cancers are hormone-positive, also referred to as estrogen receptor-positive (ER-positive). This means that the breast cancer cells are stimulated to grow from exposure to the circulating female hormones estrogen and/or progesterone.
Fortunately, several agents are approved that effectively block the cancer-stimulating effects of estrogen, including aromatase agents such as letrozole. Researchers continue to explore novel ways in which to extend the duration of anti-cancer responses with each therapy for women with advanced breast cancer.
Ribociclib is a targeted therapy that is not yet approved by the United States Food and Drug Administration (FDA). It has, however, recently received Breakthrough Therapy designation and Priority Review by the FDA, which provides the potential for a faster approval than normal, based on data demonstrating its safety and effectiveness in treating a specific disease.
Ribociclib targets two proteins called cyclin dependent kinase 4 and 6 (CDK4/6). If these proteins become over-activated, they can stimulate cancer cells to grow and divide rapidly. Ribociclib ultimately blocks or reduces the growth-stimulus caused by over-activated CDK4/6, causing cancer cells to stabilize or regress.
A phase III trial, referred to as the MONALEESA-2 trial, evaluated the effectiveness of the addition of ribociclib to letrozole among women with advanced, ER-positive breast cancer. One group of patients in this trial were treated with ribociclib plus letrozole, and one group was treated with letrozole only (standard therapy). Patients were HER2-negative. At this year’s SABCS meeting, pre-planned data from a subgroup analysis of the MONALEESA-2 trial were presented.
The first subgroup included 227 patients who had not received prior therapy for breast cancer, but had been first diagnosed once their cancer had spread from its site of origin.
- At one year, survival without progression of cancer was achieved in 82% of patients treated with ribociclib plus letrozole, compared with only 66% of patients treated with letrozole only.
The second subgroup included 393 patients who had cancer spread to only visceral sites (liver or lungs).
- Patients treated with the addition of ribociclib to letrozole achieved a 47% reduction in death or cancer progression, compared to those treated with letrozole only.
A third subgroup included 147 patients who had cancer spread to only bone-sites in the body.
- Patients treated with the addition of ribociclib to letrozole achieved a 31% reduction in death or cancer progression, compared to those treated with letrozole only.
Additional data reviewed from a subgroup analysis included patients whose cancer had spread to at least 3 different sites in the body from the original site of cancer. This group of patients also achieved a significant benefit from treatment with the addition of ribociclib to letrozole, compared to letrozole only.
The researchers concluded that the addition of ribociclib to letrozole appears to significantly improve outcomes compared to treatment with letrozole only among postmenopausal women with ER-positive, HER2-negative, advanced breast cancer. This benefit appeared to span across all subgroups evaluated, including those who had never received prior therapy for breast cancer; those whose cancer spread to visceral sites; those whose cancer spread to bone; and those whose cancer had spread to at least 3 different sites in the body.
- O’Shaughnessy J. First-line ribociclib + letrozole in patients with de novo HR+, HER2- advanced breast cancer: A subgroup analysis of the MONALEESA-2 trial. Presented at San Antonio Breast Cancer Symposium (SABCS), December 9, 2016, San Antonio, Texas (abstract # P4-22-05)
- Burris H. First-line Ribociclib + Letrozole in Patients With HR+, HER2- Advanced Breast Cancer Presenting With Visceral Metastases or Bone-only Disease: A Subgroup Analysis of the MONALEESA-2 trial. Presented at San Antonio Breast Cancer Symposium (SABCS), December 19, 2016, San Antonio, Texas (abstract # P4-22-16)