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

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• 作者：Aron Goldhirsch ; Richard D Gelber ; Martine J Piccart-Gebhart ; Ev ; ro de Azambuja ; Marion Procter ; Thomas M Suter ; Christian Jackisch ; David Cameron ; Harald A Weber ; Dominik Heinzmann ; Liss ; ra Dal Lago ; Eleanor McFadden ; Mitch Dowsett ; Michael Untch ; Luca Gianni ; Richard Bell ; Claus-Henning K?hne ; Anita Vindevoghel ; Michael Andersson ; A Murray Brunt ; et al.
• 刊名：The Lancet
• 出版年：2013
• 出版时间：21-27 September, 2013
• 年：2013
• 卷：382
• 期：9897
• 页码：1021-1028
• 全文大小：450 K

文摘

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Summary

Background

Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the m>HER2m> 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 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 , number .

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 % ] m>vsm> 275 [16¡¤3 % ] grade 3-4 adverse events, and 120 [7¡¤2 % ] m>vsm> 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).