CDK4/6 Inhibitor Extends Survival in Younger Women with HR-positive Breast Cancer
June 12th 2019
By Wayne Kuznar for oncoXchange
Chicago—Ribocliclib added to endocrine therapy (ET) represents the first treatment to demonstrate a statistically significant improvement in overall survival (OS) as initial therapy compared with ET alone in premenopausal women with hormone receptor (HR)-positive advanced breast cancer.
In the international MONALEESA-7 trial, with a median duration of follow-up of 34.6 months, patients randomized to ribociclib plus ET had a 29% relative reduction in the risk of death compared with patients randomized to ET, reported Sara Hurvitz, MD, at the 2019 ASCO annual meeting.
In the primary analysis of MONALEESA-7, as presented previously, ribociclib was shown to extend progression-free survival at a median follow-up of about 20 months.
About 20% of women diagnosed with breast cancer in the U.S. are younger than 50 years. “Compared with older women, young women with breast cancer tend to have poorer prognoses and more aggressive-behaving disease biology, even when it’s HR-positive, yet premenopausal patients are underrepresented in clinical trials,” said Dr. Hurvitz, director of the Breast Cancer Clinical Research Program at UCLA Jonsson Comprehensive Cancer Center, Los Angeles.
MONALEESA-7 is the first phase 3 study of a cyclin-dependent 4/6 kinase (CDK4/6) inhibitor to be conducted exclusively in premenopausal patients, she noted.
A total of 672 women younger than 59 years with HR-positive/HER2-negative advanced breast cancer were randomized to ribociclib or placebo plus goserelin and either a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen. Prior ET for advanced disease was not allowed but patients could have received up to one prior line of chemotherapy for metastatic disease, although this latter cohort constituted only about 15% of the total study population. Tamoxifen is no longer given with ribociclib, said Dr. Hurvitz, because of the risk of prolongation of the QT interval associated with tamoxifen in this setting.
At data cutoff (November 30, 2018), 83 patients in the ribociclib arm and 109 in the placebo arm died. Median OS was not reached in the ribocliclib plus ET arm and was 40.9 months in the placebo plus ET arm (HR 0.712; P=0.00973). Some 35% of patients in the ribociclib arm were continuing study treatment at the time of data cutoff.
In a landmark analysis, 70.2% of patients in the ribociclib arm were alive at 42 months, compared with 46.0% in the placebo arm.
Ribociclib improved OS in patients who were treated with an NSAI (median OS not reached in ribociclib arm vs. 40.7 months in the placebo arm; HR 0.699; 95% CI 0.501-0.976) or tamoxifen (HR 0.791; 95% CI 0.454-1.377).
“This is an important study because it shows that a class of drugs, CDK4/6 inhibitors, which we are widely using and have been shown to delay the time to treatment progression, delay the time to the need for chemotherapy in advanced breast cancer, and really double the effectiveness of endocrine therapy, now also translates into a significant survival benefit for women who have estrogen receptor-positive metastatic breast cancer,” commented ASCO expert Hal Burstein, MD, PhD, who was not involved in the study.
The study is also significant because estrogen receptor-positive breast cancer is the most common type of breast cancer in young women, “and this is the largest study in recent memory that has focused exclusively on premenopausal women, and shows that they too benefit from this class of drugs in a remarkable way,” he said. The survival benefit is likely a class effect, as a similar survival signal was observed with palbociclib in postmenopausal women with HR-positive breast cancer, although it narrowly missed achieving statistical significance.