HER2 Support Group Forums - Herceptin, one year V two!!

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

Prof Aron Goldhirsch MD a , Prof Richard D Gelber PhD b f, Prof Martine J Piccart-Gebhart MD c e, Evandro de Azambuja MD d e, Marion Procter MSci f, Prof Thomas M Suter MD g, Prof Christian Jackisch MD h, Prof David Cameron MD i, Harald A Weber MD j, Dominik Heinzmann PhD j, Lissandra Dal Lago MD e, Eleanor McFadden MA f, Prof Mitch Dowsett PhD k, Prof Michael Untch MD l, Luca Gianni MD m, Prof Richard Bell MD n, Prof Claus-Henning Köhne MD o, Anita Vindevoghel MD p, Michael Andersson MD q, A Murray Brunt MD r, Douglas Otero-Reyes MD s, Santai Song MD t, Prof Ian Smith MD u, Brian Leyland-Jones PhD v †, Prof Jose Baselga MD w †, for the Herceptin Adjuvant (HERA) Trial Study Team

Summary

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).