Adding Kisqali (ribociclib) to standard hormone therapy significantly extended overall survival for postmenopausal patients with HR+/HER- advanced breast cancer in the phase III MONALEESA-3 trial.
The findings also show the combination treatment is beneficial with the longest time of recurrence today in first-line therapy, and should become a first-line option in postmenopausal women with HR+/HER2- advanced breast cancer.
Dennis Slamon, chair of hematology/oncology and director of Clinical/Translational Research at the UCLA Jonsson Comprehensive Cancer Center, presented the results Sept. 29 at the 2019 European Society for Medical Oncology Congress in Barcelona.
“Many people argue 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,” Slamon said in a statement. “But we found there’s a significant difference when you use the combination of ribociclib with hormone therapy as the first line of therapy. There is absolutely no reason to wait to give women this treatment. This should be the new standard.”
This is the second phase III trial where Kisqali combination therapy met the secondary endpoint of overall survival at the pre-planned interim analysis. MONALEESA-3 evaluated efficacy and safety of Kisqali plus fulvestrant in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.
“Increasing overall survival is the hardest endpoint to move,” Slamon said. “We’re also seeing that the time of progression-free survival is the longest yet reported for any of the drugs in this class. And even when patients are off the drug, the effect seems to be long-lasting in terms of the benefit. It’s important because this means we are helping women live longer and have a better quality of life.”
The results on data previously reported by Slamon and colleagues helped lead to FDA’s approval of ribociclib. There are three CDK 4/6 inhibitors that have been approved by FDA for combination treatment with standard hormone therapies.
The double-blind clinical trial involved 726 postmenopausal women who had advanced hormone-receptor positive/HER2- breast cancer. The trial included women who had not received prior endocrine therapy as well as patients who were in the first-line or second-line setting.
The results demonstrated a statistically significant improvement in survival with a 28% reduction in risk of death. At 42 months, the estimated rates of survival were 58% for the drug combination treatment and 46% for women who were treated with the hormone therapy alone.
The median progression-free survival with ribociclib plus fulvestrant in the first-line setting is the longest reported in a phase III trial in hormone-receptor positive/HER2- breast cancer at a median of 33.6 months, compared to 19.2 months for those in the hormone therapy only group.
Kisqali in combination with fulvestrant met its secondary endpoint of overall survival, demonstrating a statistically significant improvement in survival with a 28% reduction in risk of death (median OS not reached vs. 40.0 months; HR=0.724; 95% CI: 0.568-0.924; p=0.00455).
The significant extension in survival met the early efficacy stopping criteria at a prespecified interim analysis. At 42 months, estimated rates of survival were 58% for Kisqali combination treatment and 46% for fulvestrant alone. Results in the first-line and second-line subgroups, including in patients who relapsed within 12 months of adjuvant treatment, were consistent with the overall MONALEESA-3 patient population.
Median first-line PFS was also reached at this analysis and demonstrated that Kisqali in combination with fulvestrant has a median PFS of 33.6 months compared to 19.2 months in the placebo arm (HR=0.546; 95% CI: 0.415-0.718). Additionally, the need for chemotherapy was delayed in all patients who were prescribed Kisqali plus fulvestrant (HR=0.696; 95% CI: 0.551-0.879).
Other investigators are Patrick Neven, Stephen Chia, Peter Fasching, Michelino De Laurentiis, Seock-Ah Im, Katarina Petrakova, Giulia Val Bianchi, Francisco Esteva, Miguel Martín, Arnd Nusch, Gabe Sonke, Luis De la Cruz-Merino, J. Thaddeus Beck, Xavier Pivot, Manu Sondhi, Yingbo Wang, Arunava Chakravartty, Karen Rodriguez-Lorenc, Guy Jerusalem.
The team is now evaluating these drugs in women with early-stage breast cancer in an international clinical trial called NATALEE.
The study was sponsored by Novartis, which developed ribociclib at the Novartis Institutes for BioMedical Research under a research collaboration with Astex Pharmaceuticals.
