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

Alvaro Moreno-Aspitia; Eileen M Holmes; Christian Jackisch; Evandro de Azambuja; Frances Boyle; David W Hillman; Larissa Korde; Debora Fumagalli; Miguel A Izquierdo; Ann E McCullough; Antonio C Wolff; Kathleen I Pritchard; Michael Untch; Sébastien Guillaume; Michael S Ewer; Zhimin Shao; Sung Hoon Sim; Zeba Aziz; Georgia Demetriou; Ajay O Mehta; Michael Andersson; Masakazu Toi; Istvan Lang; Binghe Xu; Ian E Smith; Carlos H Barrios; Jose Baselga; Richard D Gelber; Martine Piccart-Gebhart; ALTTO Steering Committee and Investigators

doi:10.1016/j.ejca.2021.01.053

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

Alvaro Moreno-Aspitia, Eileen M Holmes, Christian Jackisch, Evandro de Azambuja, Frances Boyle, David W Hillman, Larissa Korde, Debora Fumagalli, Miguel A Izquierdo, Ann E McCullough, Antonio C Wolff, Kathleen I Pritchard, Michael Untch, Sébastien Guillaume, Michael S Ewer, Zhimin Shao, Sung Hoon Sim, Zeba Aziz, Georgia Demetriou, Ajay O MehtaMichael Andersson, Masakazu Toi, Istvan Lang, Binghe Xu, Ian E Smith, Carlos H Barrios, Jose Baselga, Richard D Gelber, Martine Piccart-Gebhart, ALTTO Steering Committee and Investigators

Department of Oncology

19 Citations (Scopus)

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.

Original language	English
Journal	European journal of cancer (Oxford, England : 1990)
Volume	148
Pages (from-to)	287-296
Number of pages	10
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2021.01.053
Publication status	Published - May 2021

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Breast Neoplasms/drug therapy
Chemotherapy, Adjuvant/mortality
Female
Follow-Up Studies
Humans
Middle Aged
Neoadjuvant Therapy/mortality
Prognosis
Prospective Studies
Survival Rate
Young Adult
Adjuvant chemotherapy
Lapatinib
Early breast cancer
HER2
Trastuzumab

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Moreno-Aspitia, A., Holmes, E. M., Jackisch, C., de Azambuja, E., Boyle, F., Hillman, D. W., Korde, L., Fumagalli, D., Izquierdo, M. A., McCullough, A. E., Wolff, A. C., Pritchard, K. I., Untch, M., Guillaume, S., Ewer, M. S., Shao, Z., Sim, S. H., Aziz, Z., Demetriou, G., ... ALTTO Steering Committee and Investigators (2021). Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). European journal of cancer (Oxford, England : 1990), 148, 287-296. https://doi.org/10.1016/j.ejca.2021.01.053

Moreno-Aspitia, A, Holmes, EM, Jackisch, C, de Azambuja, E, Boyle, F, Hillman, DW, Korde, L, Fumagalli, D, Izquierdo, MA, McCullough, AE, Wolff, AC, Pritchard, KI, Untch, M, Guillaume, S, Ewer, MS, Shao, Z, Sim, SH, Aziz, Z, Demetriou, G, Mehta, AO, Andersson, M, Toi, M, Lang, I, Xu, B, Smith, IE, Barrios, CH, Baselga, J, Gelber, RD, Piccart-Gebhart, M & ALTTO Steering Committee and Investigators 2021, 'Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)', European journal of cancer (Oxford, England : 1990), vol. 148, pp. 287-296. https://doi.org/10.1016/j.ejca.2021.01.053

@article{d60b8b5c91184ab08df393a3324c004a,

title = "Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)",

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.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Breast Neoplasms/drug therapy, Chemotherapy, Adjuvant/mortality, Female, Follow-Up Studies, Humans, Middle Aged, Neoadjuvant Therapy/mortality, Prognosis, Prospective Studies, Survival Rate, Young Adult, Adjuvant chemotherapy, Lapatinib, Early breast cancer, HER2, Trastuzumab",

author = "Alvaro Moreno-Aspitia and Holmes, \{Eileen M\} and Christian Jackisch and \{de Azambuja\}, Evandro and Frances Boyle and Hillman, \{David W\} and Larissa Korde and Debora Fumagalli and Izquierdo, \{Miguel A\} and McCullough, \{Ann E\} and Wolff, \{Antonio C\} and Pritchard, \{Kathleen I\} and Michael Untch and S{\'e}bastien Guillaume and Ewer, \{Michael S\} and Zhimin Shao and Sim, \{Sung Hoon\} and Zeba Aziz and Georgia Demetriou and Mehta, \{Ajay O\} and Michael Andersson and Masakazu Toi and Istvan Lang and Binghe Xu and Smith, \{Ian E\} and Barrios, \{Carlos H\} and Jose Baselga and Gelber, \{Richard D\} and Martine Piccart-Gebhart and \{ALTTO Steering Committee and Investigators\}",

year = "2021",

month = may,

doi = "10.1016/j.ejca.2021.01.053",

language = "English",

volume = "148",

pages = "287--296",

journal = "European journal of cancer (Oxford, England : 1990)",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)

AU - Moreno-Aspitia, Alvaro

AU - Holmes, Eileen M

AU - Jackisch, Christian

AU - de Azambuja, Evandro

AU - Boyle, Frances

AU - Hillman, David W

AU - Korde, Larissa

AU - Fumagalli, Debora

AU - Izquierdo, Miguel A

AU - McCullough, Ann E

AU - Wolff, Antonio C

AU - Pritchard, Kathleen I

AU - Untch, Michael

AU - Guillaume, Sébastien

AU - Ewer, Michael S

AU - Shao, Zhimin

AU - Sim, Sung Hoon

AU - Aziz, Zeba

AU - Demetriou, Georgia

AU - Mehta, Ajay O

AU - Andersson, Michael

AU - Toi, Masakazu

AU - Lang, Istvan

AU - Xu, Binghe

AU - Smith, Ian E

AU - Barrios, Carlos H

AU - Baselga, Jose

AU - Gelber, Richard D

AU - Piccart-Gebhart, Martine

AU - ALTTO Steering Committee and Investigators

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Breast Neoplasms/drug therapy

KW - Chemotherapy, Adjuvant/mortality

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Middle Aged

KW - Neoadjuvant Therapy/mortality

KW - Prognosis

KW - Prospective Studies

KW - Survival Rate

KW - Young Adult

KW - Adjuvant chemotherapy

KW - Lapatinib

KW - Early breast cancer

KW - HER2

KW - Trastuzumab

UR - https://www.scopus.com/pages/publications/85102857093

U2 - 10.1016/j.ejca.2021.01.053

DO - 10.1016/j.ejca.2021.01.053

M3 - Journal article

C2 - 33765513

SN - 0959-8049

VL - 148

SP - 287

EP - 296

JO - European journal of cancer (Oxford, England : 1990)

JF - European journal of cancer (Oxford, England : 1990)

ER -

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

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Keywords

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