Jens Huober1, Eileen Holmes2, José Baselga3, Evandro de Azambuja4, Michael Untch5, Debora Fumagalli6, Severine Sarp7, Istvan Lang8, Ian Smith9, Frances Boyle10, Binghe Xu11, Christophe Lecocq4, Hans Wildiers12, Christelle Jouannaud13, John Hackman14, Lokanatha Dasappa15, Eva Ciruelos16, Juan Carlos Toral Pena17, Hryhoriy Adamchuk18, Tamas Hickish19, Lorena de la Pena20, Christian Jackisch21, Richard D Gelber22, Martine Piccart-Gebhart23, Serena Di Cosimo24. 1. University of Ulm, Breast Center, Ulm, Germany. Electronic address: jens.huober@uniklinik-ulm.de. 2. Frontier Science (Scotland) Ltd, Grampian View, Kincraig, Kingussie, United Kingdom. 3. Executive Vice President, Research & Development Oncology, AstraZeneca, United Kingdom. 4. Institut Jules Bordet and Breast European Adjuvant Study Team, Brussels, Belgium. 5. Head of Breast Cancer Center, Department of Gynecology, Gynecologic Oncology and Obstetrics, HELIOS Klinikum Berlin, Buch, Germany. 6. Breast International Group, Brussels, Belgium. 7. Novartis Pharma AG, Oncology Development Unit, Basel, Switzerland. 8. Istenhegyi Gendiagnosztika Private Health Center, Oncology Clinic, Budapest, Hungary. 9. Royal Marsden Hospital and Institute of Cancer Research, London, UK. 10. Patricia Ritchie Centre for Cancer Care and Research, The University of Sydney, Mater Hospital, North Sydney, Australia. 11. Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China. 12. KU Leuven - University of Leuven, Department of General Medical Oncology, University Hospitals Leuven, B-3000, Leuven, Belgium. 13. CRLCC Jean Godinot, Reims, France. 14. Marien-Hospital Witten, Witten, Germany. 15. Kidwai Memorial Institute of Oncology, Bangalore, India. 16. Hospital Doce de Octubre, Madrid, Spain. 17. Hospital Torrevieja-Salud, Torrevieja, Spain. 18. Krivoy Rog City Oncology Centre, Krivoy Rog, Ukraine. 19. Royal Bournemouth Hospital & Bournemouth University, Bournemouth, United Kingdom. 20. SOLTI - Breast Cancer Research Group, Barcelona, Spain. 21. Sana Klinikum Offenbach, Offenbach, Germany. 22. Department of Data Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Harvard T.H. Chan School of Public Health and Frontier Science and Technology Research Foundation, Boston, USA. 23. Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 24. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; SOLTI Breast Cancer Research Group, Barcelona, Spain.
Abstract
BACKGROUND:Lapatinib (L) plus trastuzumab (T) with weekly paclitaxel significantly increased the pathologic complete response (pCR) rate compared with the anti-human epidermal growth factor receptor 2 (HER2) agent alone plus paclitaxel. The event-free survival (EFS) and overall survival (OS) by the treatment arms L + T vs. T and L vs. T and the relationship between pCR and EFS/OS both in the whole study population and according to hormone receptor-negative and hormone receptor-positive cohorts after a median follow-up of 6.7 years were assessed. PATIENTS AND METHODS: Four hundred fifty-five patients with HER2-positive early breast cancer randomly receivedL 1500 mg/day (n = 154), T (common dose, n = 149) or L 1000 mg/day plus T (n = 152) for 6 weeks, followed by the assigned anti-HER2 treatment combined with paclitaxel weekly × 12. After surgery, patients received 3 cycles of fluorouracil, epirubicin and cyclophosphamide. The primary end-point was pCR (ypT0/is; for current analysis, it is ypT0/is ypN0), and the secondary end-points were EFS and OS. RESULTS:Six-year EFS rates were 67%, 67% and 74% with L, T and L + T, respectively (L vs T: hazard ratio [HR], 0.98 [95% confidence interval {CI}, 0.64-1.51; P = .93]; L + T vs T: HR, 0.81 [95% CI, 0.52-1.26; P = .35]). Six-Year OS rates were 82%, 79% and 85% for L, T and L + T, respectively (L vs T: HR, 0.85 [95% CI, 0.49-1.46; P = .56]; L + T vs T: HR, 0.72 [95% CI, 0.41-1.27; P = .26]). In landmark analyses, patients with a pCR had a significantly higher 6-year EFS (77% and 65%) and OS (89% and 77%) compared with those without a pCR for both overall and the hormone receptor-negative cohort. CONCLUSION: Achieving a pCR is important in HER2-positive disease and translates into better long-term outcome with regard to EFS and OS.
RCT Entities:
BACKGROUND:Lapatinib (L) plus trastuzumab (T) with weekly paclitaxel significantly increased the pathologic complete response (pCR) rate compared with the anti-human epidermal growth factor receptor 2 (HER2) agent alone plus paclitaxel. The event-free survival (EFS) and overall survival (OS) by the treatment arms L + T vs. T and L vs. T and the relationship between pCR and EFS/OS both in the whole study population and according to hormone receptor-negative and hormone receptor-positive cohorts after a median follow-up of 6.7 years were assessed. PATIENTS AND METHODS: Four hundred fifty-five patients with HER2-positive early breast cancer randomly received L 1500 mg/day (n = 154), T (common dose, n = 149) or L 1000 mg/day plus T (n = 152) for 6 weeks, followed by the assigned anti-HER2 treatment combined with paclitaxel weekly × 12. After surgery, patients received 3 cycles of fluorouracil, epirubicin and cyclophosphamide. The primary end-point was pCR (ypT0/is; for current analysis, it is ypT0/is ypN0), and the secondary end-points were EFS and OS. RESULTS: Six-year EFS rates were 67%, 67% and 74% with L, T and L + T, respectively (L vs T: hazard ratio [HR], 0.98 [95% confidence interval {CI}, 0.64-1.51; P = .93]; L + T vs T: HR, 0.81 [95% CI, 0.52-1.26; P = .35]). Six-Year OS rates were 82%, 79% and 85% for L, T and L + T, respectively (L vs T: HR, 0.85 [95% CI, 0.49-1.46; P = .56]; L + T vs T: HR, 0.72 [95% CI, 0.41-1.27; P = .26]). In landmark analyses, patients with a pCR had a significantly higher 6-year EFS (77% and 65%) and OS (89% and 77%) compared with those without a pCR for both overall and the hormone receptor-negative cohort. CONCLUSION: Achieving a pCR is important in HER2-positive disease and translates into better long-term outcome with regard to EFS and OS.
Authors: Katherine L McNamara; Jennifer L Caswell-Jin; Rohan Joshi; Zhicheng Ma; Eran Kotler; Gregory R Bean; Michelle Kriner; Zoey Zhou; Margaret Hoang; Joseph Beechem; Jason Zoeller; Michael F Press; Dennis J Slamon; Sara A Hurvitz; Christina Curtis Journal: Nat Cancer Date: 2021-04-08
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