Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial
Yet another combination to consider after CDK4/6i + ET in HR+ MBC!
In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than letrozole alone among postmenopausal patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Whether overall survival would also be longer with ribociclib was not known.
Here we report the results of the protocol-specified final analysis of overall survival, a key secondary end point. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib or placebo in combination with letrozole. Overall survival was assessed with the use of a stratified log-rank test and summarized with the use of Kaplan–Meier methods after 400 deaths had occurred. A hierarchical testing strategy was used for the analysis of progression-free survival and overall survival to ensure the validity of the findings.
After a median follow-up of 6.6 years, 181 deaths had occurred among 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group. Ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole. Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P=0.008). No new safety signals were observed.
First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo.
Yet another combination to consider after CDK4/6i + ET in HR+ MBC!
The INSEMA trial showed that for early stage, T1-T2 clinically node negative breast cancer, sentinel lymph node biopsies should not be mandatory, and best clinical judgement can be used.
Imlunestrant (novel oral SERD) was active in patients with an ESR1 mutations, but otherwise did not offer a benefit in this population of women with ER+ HER2-neg MBC. Overall survival (OS) data is pending with further follow up.
Another trial with neoadjuvant immunotherapy showing improved results over chemotherapy alone. (12% higher PCR 48% vs 36%).
Dato-DXd is now approved in HR+, HER2-neg, metastatic breast cancer after prior therapy with endocrine-based therapy and chemotherapy. There was an impressive reduction in the risk of death or progression with an HR of 0.63. Watch out for ocular and pulmonary toxicity. HER2-ultra low testing will be burdensome but must be done for drug approval.
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1 thought on “Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer”
Hi I will present further data from this trial in a Poster discussion session at ASCO in June. It will be overall survival data on patients who needed dose reductions with Ribociclib in the trial. it seems to me the drug should be considered more first line given the very strong survival data which is among the best ever seen in MBC