Updated results of HERA study: Extending trastuzumab for 2 years does not improve outcomes versus 1-year treatment

Findings confirm the current standard duration of adjuvant trastuzumab for women with HER2-positive early breast cancer

One year of adjuvant treatment with the targeted drug trastuzumab is as good as two years of treatment, for women with HER2-positive early breast cancer who have already received initial treatment with surgery, chemotherapy and radiotherapy as needed, HERA study researchers have found. The updated results of the study are reported at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

The HERA trial, which has been run by the Breast International Group (BIG) since 2001, is an international, multi-centre, phase III randomised study involving 5102 women with early HER2-positive breast cancer. After finishing primary therapy with surgery, chemotherapy and radiotherapy as indicated, they were randomly assigned to trastuzumab therapy every 3 weeks for 1 year, 2 years or observation.

As of 12 April 2012, the unadjusted hazard ratio for a woman experiencing disease relapse in the 2-year treatment arm versus the 1-year arm was 0.99 (95% CI 0.85-1.14; p = 0.8588), Prof. Richard Gelber of Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA, USA, reported. The overall survival rate in the two arms was comparable [HR=1.05 (95% CI 0.86-1.28; p = 0.6333)].

According to Prof. Gelber the key message for 2012 is that 1 year of treatment with trastuzumab remains the standard of care for HER2 positive early breast cancer patients.

The researchers found that the durable benefit in disease-free survival and overall survival of 1-year trastuzumab compared to no trastuzumab that had been reported previously remained stable at 8 years of median follow-up.

This prolonged benefit in disease-free survival and overall survival of 1-year trastuzumab over no trastuzumab is remarkably impressive and reassuring to patients, Prof. Gelber noted. These results show that the benefit of adjuvant trastuzumab remains over time and it is not lost after some years. Patients can be reassured that 1 year trastuzumab is a very effective treatment, reducing the risk of disease recurrence and death by one-quarter compared to not using trastuzumab.
 
While extending the duration of trastuzumab administration to 2 years did not significantly improve outcome compared with 1 year trastuzumab, ongoing trials are testing whether combining trastuzumab with other anti-HER2 agents (for example pertuzumab or lapatinib) might further benefit patients with HER2-positive early breast cancer.

Commenting on the data, Prof. Christoph Zielinski, Chairman of the Clinical Division of Oncology, at Medical University Vienna, Austria, who was not involved in the study, noted that the progress in the treatment of patients with early breast cancer over-expressing HER2/neu was extremely impressive and particularly successful by the introduction of trastuzumab as adjuvant treatment. This was administered in the first trials for one year and resulted in a highly significant prolongation of progression-free and overall survival. However, the question lingered whether a prolongation of treatment to two years would result in even better data than the ones obtained before.

The present trial shows that this is not the case, which strongly supports the correctness of adjuvant treatment duration delivered to patients with HER2/neu over-expressing early breast cancer. Moreover, it shows that the biology of the disease in the therapeutic interference with growth factor signalling for a period of one year cannot be improved by a longer duration of such treatment.

According to Prof. Zielinski, the oncology community can be assured that patients are being treated in the best possible and most cost-effective way, by weighing benefit versus costs for the healthcare system. The latter aspect is quite important, as the recurrence of disease in a patient leads not only to suffering and death, but also to an immensely increased burden for the society. The current data thus add to the evidence how the latter aspects can be avoided by the delivery of an optimal duration of treatment for a selected patient population.