Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer

  • Hortobagyi, Gabriel N. M.D.
  • Stemmer, Salomon M. M.D.
  • Burris, Howard A. M.D.
  • Yap, Yoon-Sim M.D.
  • Sonke, Gabe S. M.D., Ph.D.
  • Hart, Lowell M.D.
  • Campone, Mario M.D., Ph.D.
  • Petrakova, Katarina M.D., Ph.D.
  • Winer, Eric P. M.D.
  • Janni, Wolfgang M.D., Ph.D.
  • Conte, Pierfranco M.D., Ph.D.
  • Cameron, David A. M.D.
  • André, Fabrice M.D., Ph.D.
  • Arteaga, Carlos L. M.D.
  • Zarate, Juan P. M.D.
  • Chakravartty, Arunava Ph.D.
  • Taran, Tetiana M.D.
  • Le Gac, Fabienne Ph.D., Pharm.D.
  • Serra, Paolo M.Sc.
  • O'Shaughnessy, Joyce M.D.
New England Journal of Medicine 386(10):p 942-950, March 10, 2022. | DOI: 10.1056/NEJMoa2114663

Background

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.

Methods

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.

Results

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.

Conclusions

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. (Funded by Novartis; MONALEESA-2 ClinicalTrials.gov number, NCT01958021.)

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