Two UCLA-led studies have found that using the drug ribociclib in combination with a common hormone therapy may help both pre- and postmenopausal women with the most common type of breast cancer live longer than if they only receive the hormone therapy. The studies’ authors say the combination should become the first line of therapy.
Ribociclib is a cyclin-dependent kinase inhibitor that works by blocking the activity of proteins called cyclin-dependent kinases 4 and 6 enzymes. These kinases are critical in promoting cell division and growth in both normal and cancer cells. One study involved 672 women aged 25 to 59 when the study began who had advanced hormone-receptor positive/HER2- (HR+/HER2-) breast cancer. Seventy percent of the women who took the combination therapy were alive after 42 months, compared to 46 percent of women who were treated with only the hormone therapy. The other study involved 726 postmenopausal women with advanced HR+/HER2- breast cancer, and included women who had not received prior endocrine therapy as well as patients who were in the first-line or second-line setting. Results demonstrated a statistically significant improvement in survival with a 28 percent reduction in risk of death. At 42 months, the estimated rates of survival were 58 percent for the drug combination treatment and 46 percent for women who were treated with the hormone therapy alone.
The study of younger women who haven’t gone through menopause “was unique,” says Sara Hurvitz, MD, director of UCLA’s Breast Cancer Clinical Research Program and medical director of the UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit. “This is an important group to study since advanced breast cancer is the leading cause of cancer death in women 20 to 59, and the vast majority of breast cancer is hormone- receptor positive.”
None of the women in the premenopausal study had been previously treated with endocrine therapy for metastatic cancer. Half of the subjects were given hormone therapy and a placebo. The other half received hormone therapy in addition to ribociclib. In the postmenopausal study, the findings showed that the combination treatment is beneficial at the time of recurrence or after progression of disease in the second-line setting and, thus, endocrine therapy plus a cyclin-dependent kinase 4/6 (cdk-4/6) inhibitor should become the standard first- or second-line option in postmenopausal women with HR+/HER2- advanced breast cancer.
Hormone therapy, also called endocrine therapy, is an essential part of treatment for hormone-receptor positive breast cancer, a form of the disease in which a woman’s own hormones promote cancer growth. Given as an oral medication, the therapy works by blocking or lowering the levels of estrogen production so cancer cells can’t use them to grow and spread — but it eventually stops working in some women.
Among women who received the combination therapy in the premenopausal study, the disease did not progress for an average of 23.8 months, compared to 13 months for those who received endocrine therapy and the placebo. “It’s great to see that we’re extending the length of someone’s life, not just the length of time their disease is controlled,” Dr. Hurvitz says. “Very few trials show an improvement in overall survival. That’s what is so phenomenal about the data.”
From 1976 to 2009, the incidence of advanced breast cancer among U.S. women under 40 increased an average of about 2 percent per year, a larger increase than for any other age group. In the mid-2000s, a team of Jonsson Cancer Center researchers led by Dennis Slamon, MD, PhD, director for clinical/translational research in the cancer center, were on the forefront of discovering that the cdk-4/6 inhibitors are effective in treating hormone receptor positive breast cancer. Their work ultimately helped lead to the FDA approval of ribociclib and two other related cdk-4/6 inhibitors to treat metastatic breast cancer.
“Many people had argued that the first type of treatment women with this type of metastatic cancer should receive is some other form of hormonal therapy and then wait to see if they respond to that treatment,” Dr. Slamon says. “But we found there’s a significant improvement in survival when you use the combination of ribociclib with hormone therapy as the first line of therapy. There now is absolutely no reason to wait to give women this treatment. This should be the new standard of care.”
Read more information about the Phase III clinical trial of ribociclib and enrollment
Read an abstract in the Journal of Clinical Oncology about the ribociclib-plus-endocrine therapy