Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). (May 2021)

• Record Type: Journal Article
• Authors: Moreno-Aspitia, Alvaro; Holmes, Eileen M.; Jackisch, Christian; de Azambuja, Evandro; Boyle, Frances; Hillman, David W.; Korde, Larissa; Fumagalli, Debora; Izquierdo, Miguel A.; McCullough, Ann E.; Wolff, Antonio C.; Pritchard, Kathleen I.; Untch, Michael; Guillaume, Sébastien; Ewer, Michael S.; Shao, Zhimin; Sim, Sung Hoon; Aziz, Zeba; Demetriou, Georgia; Mehta, Ajay O.; Andersson, Michael; Toi, Masakazu; Lang, Istvan; Xu, Binghe; Smith, Ian E.; Barrios, Carlos H.; Baselga, Jose; Gelber, Richard D.; Piccart-Gebhart, Martine; Hilbers, Florentine; El-Abed, Sarra; Balta, Vasiliki; Schurmans, Celine; Rosa, Daniela D.; Saini, Kamal; Filho, Otto Metzger; McConnell, Robin; Paterson, Vicki; Campbell, Christine; McFadden, Eleanor; Paterson, Emma; Kassab, Garrick;
• Is Part Of: European journal of cancer. Volume 148(2021)
• Page Start: 287
• Page End: 296
• Publication Date: 2021-05
• Subjects: Early breast cancer -- HER2 -- Lapatinib -- Trastuzumab -- Adjuvant chemotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.01.053
• Languages: English
• ISSNs: 0959-8049

Abstract

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 . Highlights: Revised with under 85 characters with spaces. First phase III study of adjuvant dual HER2 blockade for HER2+ breast cancer (77 characters including spaces). 8381 patients with stage I-III HER2+ breast cancer, followed for at least 5 years (82 characters including spaces). Compared chemotherapy + trastuzumab versus chemotherapy + 3 lapatinib-containing arms (82 characters including spaces). Lapatinib associated with increased non-cardiac toxicity (57 characters including spaces). Chemotherapy + lapatinib/trastuzumab not superior to chemotherapy + trastuzumab (80 characters including spaces).