LBA7 - Disease-free survival (DFS) in the lapatinib alone arm and expanded results of the phase III ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D) in the...

Date 29 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Presenter Edith Perez
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors E.A. Perez1, E. Holmes2, E. De Azambuja3, A. Dueck4, J. Baselga5, G. Viale6, J.A. Zujewski7, A. Goldhirsch8, R. Crescenzo9, K. Pritchard10, A.C. Wolff11, C. Jackisch12, I. Láng13, M. Untch14, I. Smith15, F. Boyle16, B. Xu17, H.L. Gomez18, R.D. Gelber19, M. Piccart20
  • 1Hematology / Oncology, Mayo Clinic, 32224 - Jacksonville/US
  • 2Statistics, Frontier Science (Scotland) Ltd, Kincraig/GB
  • 3Medical Oncology, Institute Jules Bordet, 1000 - Brussels/BE
  • 4Section Of Biostatistics, Mayo Clinic, Scottsdale/US
  • 5Hematology Oncology, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 6Department Of Pathology, Istituto Europeo di Oncologia, 20141 - Milan/IT
  • 7Breast Cancer Therapeutics, National Cancer Institute, Bethesda/UM
  • 8Department Of Medicine, European Institute of Oncology, 20141 - Milan/IT
  • 9Hematology/oncology, GlaxoSmithKline, Collegeville/US
  • 10Medical Oncology, Sunnybrook Odette Cancer Center, CA-M4N 3M5 - Toronto/CA
  • 11Department Of Oncology, Johns Hopkins University, US-21231 - Baltimore/US
  • 12Oncology, Klinikum Offenbach GmbH, Offenbach/DE
  • 13Dept. Med. Oncology And Clin. Pharmacology B, National Institute of Oncology, HU-1122 - Budapest/HU
  • 14Chefarzt Der Frauenklinik, HELIOS Klinikum Berlin-Buch, 13125 - Berlin/DE
  • 15Medical Oncology, Royal Marsden Hospital NHS Trust, Surrey/GB
  • 16Medical Oncology, Patricia Ritchie Centre for Cancer Care and Research, The University of Sydney, Mater Hospital, North Sydney/AU
  • 17Medical Dept., Cancer Hospital, Chinese Academy of Medical Sciences, 100021 - Beijing/CN
  • 18Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima/PE
  • 19Biostatistics And Computational Biology, Dana Farber Cancer Institute, US-02215 - Boston/US
  • 20Medicine, Institute Jules Bordet, 1000 - Brussels/BE

Abstract

Aim

The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial is a randomised phase III adjuvant breast cancer trial comparing 3 oral lapatinib (L)-containing regimens with trastuzumab (T), each given for 1 year. DFS results of L + T and T—> L compared to T, presented at ASCO 2014, showed a non-significant DFS benefit. Results of L vs T and key secondary analyses are presented for the first time.

Methods

8381 patients (pts) were randomised to receive either T (N=2097), L (N=2100), T —> L (N=2091), or L + T (N=2093) from 2007-2011. Primary comparison of L vs T evaluated non-inferiority at a margin of 1.11 and the futility boundary for this arm was crossed resulting in premature arm closure (Aug 2011). Pts in the L arm who were free of disease recurrence at that time were offered T as adjuvant treatment. Key secondary analyses including DFS by hormone receptor status and CNS endpoints are now presented.

Results

In 4197 pts and at a median follow-up of 4.5 years, 366 (17%) DFS events in the L and 301 (14%) DFS events in the T arms were observed. 1090 (52%) pts in the L arm received at least one T dose. In post-hoc analysis, there was evidence that these pts benefitted from receiving T [hazard ratio (HR) = 0.67; 95% CI 0.49-0.91 from a time-dependent Cox model of DFS]. The non-inferiority HR was 1.34 (95% CI 1.15-1.56) in the ITT population; 1.45 for hormone receptor negative, 1.23 for hormone receptor positive. CNS as first site of metastases occurred in 2% of cases in all arms. AEs of any grade were more common with L than T: diarrhoea (64% vs 20%), rash or erythema (54% vs 20%) and hepatobiliary (25% vs 16%). Any cardiac events were infrequent in both arms, but more common in T compared to L (4.5% vs 1.9%; p <0.0005), although the rate of protocol defined primary cardiac events was <1% for all arms.

Conclusions

Overall, L added to T did not statistically improve DFS. L did not appear to decrease the rate of CNS as first site of metastases. T confers a better outcome compared to L in pts with HER2-positive EBC and remains the standard of care. There is evidence of T benefit even when initiated later in the course of follow-up.

Disclosure

E. De Azambuja: Disclosed an advisory role with GSK; honoraria from Roche; research funding from GSK; and travel grants from GSK/Roche; G. Viale: disclosed an advisory role with Roche and Dako; and honoraria from GSK, Roche, and Dako; R. Crescenzo: disclosed compensated employment with GlaxoSmithKline; and stock ownership with Glaxo SmithKline; K. Pritchard: disclosed an advisory role with Roche; honoraria from Roche; research funding from Roche; and expert testimony on behalf of Roche; C. Jackisch: disclosed honoraria from Roche and GSK; F. Boyle: disclosed honoraria from GlaxoSmithKline; and research funding from GlaxoSmithKline; R.D. Gelber: disclosed research funding from GSK and Roche; M. Piccart: disclosed consultancy with PharmaMar; honoraria from Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, MSD, Novartis, Pfizer, Roche-Genentech, Sanofi Aventis, Symphogen, Synthon, and Verastem; research grants from most companies. All other authors have declared no conflicts of interest.