Multicenter phase 2 trial of neoadjuvant atezolizumab plus dual HER2 blockade plus epirubicin for women with early HER2-positive breast cancer

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. The multicenter phase 2 ABCSG-52 trial in Austria evaluated epirubicin plus immunotherapy in women with HER2-positive EBC. A total of 58 patients were randomized 1:1 to two cycles of a chemotherapy-free induction phase (part 1) of dual HER2 blockade with trastuzumab and pertuzumab (TP) plus atezolizumab (A-TP) or TP alone. Thereafter, all patients received four cycles of TP-A plus epirubicin (part 2). The primary end point, pathological complete response, was met in 35 patients (60.3%; 95% CI 47.5-71.9): 65.5% of patients in the TP-A group and 55.2% of patients in the TP group. The residual cancer burden 0/1 rate was 80.0% (95% CI 67.7-88.4) and the objective response rate was 89.3% (78.5-95.0). Grade ≥ 3 adverse events were reportedn in 17 patients (29.3%). The authors conclude that a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is effective and safe in patients with HER2-positive EBC.