HERA Trial: Long-term Results of 1 year of Trastuzumab verses 2 years of Trastuzumab Treatment in HER2-positive Early Breast Cancer

6 Apr, 21

Introduction

Trastuzumab is a recombinant monoclonal antibody against HER2 receptor. It significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer. However long-term data is lacking.

Aim

HERA (HERceptin Adjuvant) trial compared the year of trastuzumab, and 2 years of trastuzumab treatment at a median follow-up of 11 years in HER2-positive early breast cancer

Patient Profile

N=5102
Women with HER2-positive early breast cancer

Methods

Multicentre, open-label, phase 3 randomised trial

Clinical and laboratory assessments were scheduled to occur every 6 months for years 3–5, and then once per year up to year 10
Annual chest radiography was required up to year 5 and annual mammography up to year 10

Endpoints

Primary endpoint was disease-free survival, and analyses are in the intention-to-treat population
Comparison of 2 years versus 1 year of trastuzumab is based on 366-day landmark analyses
Secondary endpoints included
- Overall survival
- Sites of first relapse
- Competing-risk cumulative incidence analysis of breast cancer a
- Non-breast cancer disease free survival events
- Cardiac safety

Results

In 1 year of trastuzumab group, the median follow-up of 11 years showed significant reduction in the risk of a disease-free survival event (HR 0·76,) and death (0·74, 0·64–0·86) compared with observation

2 years of adjuvant trastuzumab did not improve disease free-survival outcomes compared with 1 year of this drug (HR 1·02)

Figure 1: Estimates of 10-year disease-free survival

24% relative reduction in risk of a disease-free survival event, and a 26% relative reduction in risk of death was observed with the addition of 1 year of adjuvant trastuzumab in women with HER2-positive early breast cancer

Cardiac Toxicity

Cardiac toxicity remained low in all groups and occurred mostly during the treatment phase

No significant difference was noted in the occurrence of primary cardiac endpoints between the two trastuzumab groups
Secondary cardiac endpoints occurred more frequently in the 2-years trastuzumab group than in the 1-year trastuzumab group and the observation group

Table 1: Incidence of cardiac toxicity

	1-year trastuzumab group	2-year trastuzumab group	Observation group
Primary Cardiac endpoints	1%	1%	0.1%
Secondary cardiac endpoints	7.3%	4.4%	0.9%

Subgroup analysis of disease-free survival by nodal status showed the 10-year disease-free survival in

1-year trastuzumab group: 80% for the node-negative cohort, 75% for the cohort with one to three positive nodes, and 55% for the cohort with four or more positive nodes
HRs (1-year trastuzumab vs observation) were 0.78 for the node-negative cohort, 0.64 for those with one to three positive nodes, and 0.82 in those with four or more positive nodes

Conclusion

The HERA trial demonstrated that the addition of 1 year of adjuvant trastuzumab in women with HER2-positive early breast cancer resulted in
- 24% relative reduction in risk of a disease-free survival event
- 26% relative reduction in risk of death
The HERA study therefore shows that 1 year of trastuzumab is an important, and curative, part of the standard of care for women with HER2-positive early breast cancer.

Reference

Lancet.2017;389(10075):1195-1205