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Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.

Gabriel N Hortobagyi1, Salomon M Stemmer1, Howard A Burris1

  • 1From the Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.N.H.), and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center (C.L.A.), and Baylor University Medical Center, Texas Oncology, US Oncology (J.O.), Dallas - all in Texas; the Institute of Oncology, Davidoff Center, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel (S.M.S.); Sarah Cannon Research Institute, Nashville (H.A.B.); the Department of Medical Oncology, National Cancer Centre Singapore, Singapore (Y.-S.Y.); the Department of Medical Oncology, Netherlands Cancer Institute and Borstkanker Onderzoek Groep Study Center, Amsterdam (G.S.S.); Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers (L.H.); the Department of Medical Oncology, Institut de Cancérologie de l'Ouest-René Gauducheau, Saint-Herblain (M.C.), and the Department of Medical Oncology, Institut Gustave Roussy, Medical School, Université Paris-Saclay, Villejuif (F.A.) - both in France; the Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic (K.P.); the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston (E.P.W.); the Department of Gynecology, University of Ulm, Ulm, Germany (W.J.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and the Division of Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padua, Italy (P.C.); the Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh (D.A.C.); Novartis Pharmaceuticals, East Hanover, NJ (J.P.Z., A.C.); and Novartis Pharma, Basel, Switzerland (T.T., F.L.G., P.S.).

The New England Journal of Medicine
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First-line ribociclib plus letrozole significantly improved overall survival in postmenopausal patients with advanced HR+, HER2- breast cancer. This combination therapy demonstrated a median overall survival benefit of over 12 months compared to placebo plus letrozole.

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Area of Science:

  • Oncology
  • Clinical Trials
  • Pharmacology

Background:

  • Previous analysis showed ribociclib plus letrozole improved progression-free survival in HR+, HER2- advanced breast cancer.
  • Overall survival (OS) benefit of this combination was previously unknown.

Purpose of the Study:

  • To report the final overall survival (OS) analysis from a phase 3 trial of first-line ribociclib plus letrozole versus placebo plus letrozole.
  • To evaluate the efficacy and safety of ribociclib in combination with letrozole for advanced HR+, HER2- breast cancer.

Main Methods:

  • Phase 3, randomized, double-blind trial comparing ribociclib plus letrozole to placebo plus letrozole.
  • Overall survival (OS) was a key secondary endpoint, assessed using stratified log-rank test and Kaplan-Meier methods after 400 deaths.
  • Hierarchical testing strategy ensured validity of progression-free survival and OS analyses.

Main Results:

  • Median follow-up was 6.6 years, with 181 deaths in the ribociclib group (54.2%) and 219 in the placebo group (65.6%).
  • Ribociclib plus letrozole demonstrated a significant overall survival (OS) benefit (HR: 0.76; P = 0.008).
  • Median OS was 63.9 months with ribociclib plus letrozole versus 51.4 months with placebo plus letrozole, a difference of over 12 months.

Conclusions:

  • First-line ribociclib plus letrozole offers a significant overall survival (OS) benefit in advanced HR+, HER2- breast cancer.
  • The combination therapy is a valuable treatment option, showing a substantial increase in median OS.
  • No new safety concerns were identified with the addition of ribociclib.