2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial.

Abstract

BACKGROUND:

Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial.

METHODS:

The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant chemotherapy, adjuvant chemotherapy, or both in 5102 patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. The comparison of 2 years versus 1 year of trastuzumab treatment involved a landmark analysis of 3105 patients who were disease-free 12 months after randomisation to one of the trastuzumab groups, and was planned after observing at least 725 disease-free survival events. The updated intention-to-treat comparison of 1 year trastuzumab treatment versus observation alone in 3399 patients at a median follow-up of 8 years (range 0-10) is also reported. This study is registered with ClinicalTrials.gov, number NCT00045032.

FINDINGS:

We recorded 367 events of disease-free survival in 1552 patients in the 1 year group and 367 events in 1553 patients in the 2 year group (hazard ratio [HR] 0·99, 95% CI 0·85-1·14, p=0·86). Grade 3-4 adverse events and decreases in left ventricular ejection fraction during treatment were reported more frequently in the 2 year treatment group than in the 1 year group (342 [20·4%] vs 275 [16·3%] grade 3-4 adverse events, and 120 [7·2%] vs 69 [4·1%] decreases in left ventricular ejection fraction, respectively). HRs for a comparison of 1 year of trastuzumab treatment versus observation were 0·76 (95% CI 0·67-0·86, p<0·0001) for disease-free survival and 0·76 (0·65-0·88, p=0·0005) for overall survival, despite crossover of 884 (52%) patients from the observation group to trastuzumab therapy.

INTERPRETATION:

2 years of adjuvant trastuzumab is not more effective than is 1 year of treatment for patients with HER2-positive early breast cancer. 1 year of treatment provides a significant disease-free and overall survival benefit compared with observation and remains the standard of care.

FUNDING:

F Hoffmann-La Roche (Roche).

• Authors: Aron Goldhirsch, Richard D Gelber, Martine J Piccart-Gebhart, Evandro de Azambuja, Marion Procter, Thomas M Suter, Christian Jackisch, David Cameron, Harald A Weber, Dominik Heinzmann, Lissandra Dal Lago, Eleanor McFadden, Mitch Dowsett, Michael Untch, Luca Gianni, Richard Bell, Claus-Henning Köhne, Anita Vindevoghel, Michael Andersson, A Murray Brunt, Douglas Otero-Reyes, Santai Song, Ian Smith, Brian Leyland-Jones, Jose Baselga, Herceptin Adjuvant (HERA) Trial Study Team
• Journal: Lancet (London, England) (Lancet) Vol. 382 Issue 9897 Pg. 1021-8 (Sep 21 2013) ISSN: 1474-547X [Electronic] England
• PMID: 23871490 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Receptor, ErbB-2
• Trastuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Agents (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Medication Adherence
• Middle Aged
• Receptor, ErbB-2 (metabolism)
• Trastuzumab
• Treatment Outcome