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Ribociclib plus Endocrine Therapy in Early Breast Cancer
Dennis Slamon1, Oleg Lipatov1, Zbigniew Nowecki1
1From the David Geffen School of Medicine at the University of California, Los Angeles (D. Slamon, N.M.); Republican Clinical Oncology Dispensary, Ufa (O.L.), and Moscow City Oncology Hospital No. 62, Moscow (D. Stroyakovskiy) - both in Russia; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw (Z.N.), and Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli, Lublin (B.K.-B.) - both in Poland; the Sarah Cannon Research Institute at Tennessee Oncology, Nashville (D.A.Y.); the National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City (C.-S.H.); University Hospital Erlangen, the Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), and the Interdisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin (M.U.) - both in Germany; St. Vincent's Hospital, Dublin (J.C.); Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston (A.B.); the British Columbia Cancer Agency, Vancouver (S.C.), and Translational Research in Oncology (TRIO), Edmonton, AB (I.S.) - both in Canada; the Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); Hospital Virgen del Rocío, Seville, and Grupo Español de Investigación en Cáncer de Mama, Spanish Breast Cancer Group, Madrid - both in Spain (M.R.-B.); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (S.L.); the Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (B.X.); the Fred Hutchinson Cancer Center, University of Washington, Seattle (S.H.); the Latin American Cooperative Oncology Group, Porto Alegre, Brazil (C.B.); the Orlando Health Cancer Institute, Orlando, FL (R.M.); the National Breast Cancer Coalition, Washington, DC (F.V.); TRIO, Paris (K.A.); TRIO, Montevideo, Uruguay (R.F.); Novartis Pharmaceuticals, East Hanover, NJ (Y.J., F.G., Z.L., J.P.Z., A.C.); Novartis Pharma, Basel, Switzerland (T.T.); and the Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.H.).
Background:
Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.
Methods:
In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy.
Results:
As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals.
Conclusions:
Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).
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