Ribociclib plus fulvestratnt has the longest mOS OF over 67 months in postmenopausal breast cancer patients

05 Jul 2022

Cancer is a leading cause of death globally, claiming almost 10 million deaths in 2020.1 Breast cancer is one of the most common cancers in women, with nearly 2.3 million new breast cancer diagnoses in 2020 worldwide.1 Gene-expression profiling has identified distinct subtypes of cancer, among which there are subpopulations expressing specific markers.2 According to the National Institutes of Health (NIH), hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) is the most prevalent breast cancer.3 Cyclin-dependent kinase 4 and 6 (CDK4/6) are good drug targets for cancer, owing to their role in cell cycle progression.4 Ribociclib is one of the 3 inhibitors of CDK4/6 approved in combination with fulvestrant for treating HR+/HER2- advanced breast cancers in adults, based on a series of phase 3 clinical trials called MONALEESA, which tested ribociclib along with different drug partners in HR+/HER2- cancer patients.4-7 The MONALEESA-2 study showed that progression-free survival (PFS) was significantly longer with first-line ribociclib + letrozole than with placebo + letrozole.7 The MONALEESA-7 trial also showed significantly longer median overall survival (mOS) in ribociclib in combination with the endocrine therapy (ET) vs. the placebo arm in postmenopausal HR+/HER2- cancer patients.6 Similarly, the primary MONALEESA-3 trial and its subsequent analysis Demonstrated that ribociclib + fulvestrant had significant OS benefit as compared with placebo in HR+/HER2- patients advanced breast cancer patients.5,6 In a recently held European Society of Medical Oncology (ESMO) Breast Cancer Congress, Neven, et al. presented an updated exploratory mOS analysis result with the longest follow-up of the MONALEESA 3 study to date.8

This analysis was a randomized, placebo-controlled, double-blind, multicenter phase 3 trial, recruiting postmenopausal women with HR+/HER2- advanced breast cancer who were ET naive or had received 1 line of ET for advanced breast cancer, or had a relapse within the past 12 months of ET and received treatment in the first-line setting.6,8 Patients receiving first-line treatment were those with de novo disease or relapse >12 months from the completion of (neo) adjuvant ET.6 Patients who had received prior chemotherapy or therapy with fulvestrant or any other CDK4/6 inhibitors were excluded.6 Patients were randomized 2:1 to receive either ribociclib + fulvestrant (n=237) or placebo + fulvestrant (n=128) as first-line therapy.6

The median follow-up of first-line patients was 70.8 months at a cut-off date of January 12, 2022, and about 16.5% and 8.6% of patients were still on treatment in the ribociclib and placebo arms, respectively.8 There was a significant mOS benefit in the ribociclib group vs. the placebo group (67.6 vs. 51.8 months, respectively; HR=0.67; 95% CI: 0.50-0.90).8 The overall survival (OS) rate at 5 years was better in the ribociclib arm than the placebo arm (56.5% vs. 42.1%, respectively).8 Similarly, PFS2 (HR=0.64) and chemotherapy-free survival (HR=0.62) were longer in the ribociclib group than in the placebo group.8 Among those who discontinued the treatment, more patients in the placebo group required antineoplastic therapy or subsequent CDK4/6 inhibitor treatment than in the ribociclib group.8 A total of 89.7% vs. 81.8% received neoplastic treatment, and 35.5% vs. 16.7% received CDK4/6 inhibitors in the placebo vs. the ribociclib group, respectively.8 Results of the intention-to-treat and second-line population were similar to the previous analysis.8

This exploratory analysis of the first-line therapy population in the MONALEESA-3 trial with additional follow-up showed that there was a significant mOS benefit of almost 16 months and a 33% relative reduction in the risk of death with ribociclib + fulvestrant as compared with fulvestrant alone.8 These results are significant in supporting the ribociclib + fulvestrant regimen as first-line therapy in HR+/HER2- advanced breast cancer patients.8

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