A growing body of evidence demonstrates that the immune system contributes to the therapeutic effects of trastuzumab. We sought to determine whether autoimmune background could identify patients with HER2 positive early breast cancer (EBC) who derive differential benefit from adjuvant primary trastuzumab-based therapy.
HERA (BIG 1-01) is an international, multicenter, open-label, phase 3 randomized trial of 5,102 women with HER2-positive EBC, who were enrolled after completion of their postoperative chemotherapy to receive trastuzumab for 1 year, 2 years, or no trastuzumab. In this exploratory analysis, we evaluated whether there is an interaction between autoimmune history and the magnitude of trastuzumab benefit with respect to disease-free survival (DFS) and overall survival (OS).
A total of 5,099 patients were included in the current analysis: 4,774 patients (93.6%) had no history of autoimmune disease at baseline while 325 patients (6.4%) had autoimmune disease history, 295 of whom had active disease. Median follow-up was 11 years (IQR 10.09–11.53); 1,631 patients experienced a DFS event and 1,037 patients experienced an OS event. Random assignment to 1 or 2 years of trastuzumab compared with no trastuzumab yielded similar reductions in the risk of events for patients with no autoimmune history as for patients with autoimmune history (interaction p = 0.95 for DFS, and p = 0.62 for OS). Trastuzumab reduced the risk of DFS event for both the no autoimmune (HR 0.77, 95% CI 0.69–0.85) as well as the autoimmune history group (HR 0.76, 95% CI 0.51–1.12). The risk of death was also similarly reduced for both groups: no autoimmune history: (HR 0.74, 95% CI 0.65-0.84); autoimmune history: (HR 0.65, 95% CI 0.40-1.07).
We found no evidence of a differential benefit from trastuzumab in patients with a medical history of autoimmune disease.
Clinical trial identification
Legal entity responsible for the study
BrEAST - Amir Sonnenblick.
HERA was conducted under the umbrella of the Breast international group (BIG), with sponsorship and funding provided by F Hoffmann-La Roche.
C. Jackisch: Advisory board: Roche; Travel grants: Roche. D. Zardavas: Research grants; Roche, Genentech, Pfizer, AstraZeneca. N. Al-Sakaff: Employment: F. Hoffmann-La Roche. R. Gelber: Contributions to clinical trials: Roche, Novartis, Pfizer, AstraZeneca, Ipsen, Ferring, GSK, Celgene. M. Piccart: Consultancy fees: Roche. E. de Azambuja: Research grant, Advisory board and honoraria: Roche; Travel grants: Roche / GSK. All other authors have declared no conflicts of interest.