Another landmark study supporting the use CDK4/6 drugs along with endocrine therapy in the breast cancer metastatic setting. Missed opportunities insofar as adding CDK 4/6 drugs to endocrine blockade are a concern, since the OS survival difference is significant.
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.
MammaPrint did not predict distant recurrence, but it did predict patients who may benefit from extended hormonal therapy. We do have breast index, so now we have options. Breast index can predict the possibility of recurrence though by helping to determine the level of risk.
Adding Inavolisib to CKD4/6 inhibitor and AI improved progression-free survival (almost doubled 15 vs 7m) but toxicity was higher still in the single digits (hyperglycemia, diarrhea, stomatitis… all less than 6% G3/4).
Well done study showing a 20% decrease in recurrence risk when using dose dense therapy [EC]/D compared to conventional dose [FEC]/D. Sometimes it is worth it to push.
Myth busted. In aggressive breast cancer, no need to start chemotherapy now, ET and CKD4/6 inhibitors are better tolerated with significant progression-free survival (PFS) benefit and same response rate.
It seems donepezil did not show any cognitive benefit when added to standard adjuvant chemotherapy for breast cancer. Unfortunately, adequate treatment for ‘chemo-brain’ remains elusive. There is data that a lipid structure, S1P, may be linked to this process and may be ‘druggable’ with some of the MS agents.
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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