Alvaro Moreno-Aspitia1, Eileen M Holmes2, Christian Jackisch3, Evandro de Azambuja4, Frances Boyle5, David W Hillman6, Larissa Korde7, Debora Fumagalli8, Miguel A Izquierdo9, Ann E McCullough10, Antonio C Wolff11, Kathleen I Pritchard12, Michael Untch13, Sébastien Guillaume4, Michael S Ewer14, Zhimin Shao15, Sung Hoon Sim16, Zeba Aziz17, Georgia Demetriou18, Ajay O Mehta19, Michael Andersson20, Masakazu Toi21, Istvan Lang22, Binghe Xu23, Ian E Smith24, Carlos H Barrios25, Jose Baselga26, Richard D Gelber27, Martine Piccart-Gebhart4. 1. Jacoby Center for Breast Health, Mayo Clinic, Jacksonville, FL, USA. Electronic address: morenoaspitia.alvaro@mayo.edu. 2. Dundee Epidemiology and Statistics Unit, University of Dundee, Dundee, UK. 3. Department of Gynecology and Obstetrics, Sana Klinikum Offenbach GmbH, Offenbach am Main, Germany. 4. Institute Jules Bordet and l' Université Libre de Bruxelles (U.L.B), Brussels, Belgium. 5. Patricia Ritchie Centre for Cancer Care and Research, University of Sydney, Sydney, Australia. 6. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA. 7. Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. 8. Breast International Group, Brussels, Belgium. 9. Novartis Pharma AG, Basel, Switzerland. 10. Division of Anatomic Pathology, Mayo Clinic, Scottsdale, AZ, USA. 11. Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA. 12. Canadian Cancer Trials Group (CCTG), Kingston, Ontario, Canada. 13. Helios Klinikum Berlin-Buch, Berlin, Germany. 14. MD Anderson Cancer Center, University of Texas, Houston, TX, USA. 15. Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. 16. Center for Breast Cancer, National Cancer Centre, Gyeonggi-do, South Korea. 17. Allama Iqbal Medical College, Lahore, Pakistan. 18. University of the Witwatersrand, Johannesburg, South Africa. 19. Central India Cancer Research Institute, Nagpur, Maharashtra, India. 20. Department of Oncology, Rigshospitalet, Copenhagen, Denmark. 21. Graduate School of Medicine, Kyoto University, Kyoto, Japan. 22. National Institute of Oncology, Budapest, Hungary. 23. National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China. 24. The Royal Marsden Hospital NHS Foundation Trust, London, UK. 25. Latin American Cooperative Oncology Group (LACOG), Oncoclínicas, Porto Alegre, Brazil. 26. Oncology Research and Development, Astra-Zeneca, Cambridge, UK. 27. Dana-Farber Cancer Institute, Harvard Medical School, Harvard TH Chan School of Public Health and Frontier Science Technology Research Foundation, Boston, MA, USA.
Abstract
AIM: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial. PATIENTS AND METHODS: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac). RESULTS: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups. CONCLUSION: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00490139.
AIM: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial. PATIENTS AND METHODS: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac). RESULTS: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups. CONCLUSION: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00490139.
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