The MONALEESA-7 trial tested the combination of ribociclib with endocrine therapy in premenopausal women with advanced HR-positive/HER2-negative breast cancer.
CHICAGO-Combining the cyclin-dependent kinase (CDK) inhibitor ribociclib with standard-of-care endocrine therapy may significantly improve overall survival in premenopausal women with advanced hormone receptor (HR)-positive/HER2-negative breast cancer compared with endocrine therapy alone, according to the latest data from the international phase III MONALEESA-7 trial (abstract LBA1008) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
Researchers found that 70.2% of the women who took the combination therapy were alive after 42 months compared with 46.0% of women who were treated with only the hormone therapy. Lead study author Sara A. Hurvitz, MD, director of the Breast Cancer Clinical Research Program at UCLA Jonsson Comprehensive Cancer Center in Los Angeles, said these data are the first to show improved overall survival for any targeted therapy when used with endocrine therapy as a first-line treatment for advanced breast cancer. “I was very happy to see that the benefits of ribociclib therapy are actually far-reaching, beyond the time the patient is receiving that therapy,” she said.
The study involved 672 women (under age 59) who received goserelin (an injectable endocrine therapy) and one of three other therapies (letrozole, anastrozole, or tamoxifen). None of the women had received prior endocrine therapy; 173 (26%) women were still receiving the therapies after a median follow-up of 34.6 months, with 116 (35%) still receiving ribociclib and 57 (17%) still receiving the placebo.
Among women who received the combination therapy, the disease did not progress for an average of 23.8 months compared with 13 months for those who received endocrine therapy alone. Overall, the combination therapy group experienced a 29% relative reduction in the risk of death. The overall survival rate was 71% for women who took ribociclib in combination with tamoxifen and 70% for women who took ribociclib in combination with a nonsteroidal aromatase inhibitor. The survival rate was 55% for women receiving tamoxifen alone and 43% for women receiving a nonsteroidal aromatase inhibitor alone.
Ribociclib was generally well tolerated. “The safety profile we are presenting is in line with that which was published last year. No new safety signals were identified. The most common grade 3/4 side effect was neutropenia,” noted Hurvitz.
From 1976 to 2009, the incidence of advanced breast cancer among US women under age 40 increased an average of about 2% per year, a larger increase than for any other age group, according to the study authors. “The most common type of breast cancer is HR-positive, thus these data apply to the majority of breast cancer patients with stage IV disease. This study exclusively evaluated younger women (< 59 years, pre/perimenopausal), a patient population that may have more aggressive disease biology,” said Hurvitz.
The researchers are now conducting subanalyses to try to identify biomarkers and circulating tumor DNA that may indicate which women might benefit the most from ribociclib.
Maysa Abu-Khalaf, MD, director of the Breast Medical Oncology Program and co-director of the Breast Care Center at the Sidney Kimmel Cancer Center-Jefferson Health in Philadelphia, told Cancer Network that ribociclib is one of three US Food and Drug Administration–approved CDK4/6 inhibitor drugs that have been shown to significantly prolong progression-free survival (PFS) in patients with HR-positive advanced breast cancer. She said that what is unique about the MONALEESA-7 study design is that it only enrolled premenopausal women with HR-positive advanced breast cancer who received goserelin to suppress their ovarian function.
“Breast cancer is known to be much more aggressive in younger premenopausal women compared to postmenopausal women, so it is great to see that adding ribociclib to endocrine therapy can actually result in a significant improvement in overall survival in these young patients. In general, it is not common for clinical trials to demonstrate a survival advantage in this setting, so these results are impressive,” said Abu-Khalaf.