The addition of atezolizumab does not improve the efficacy of standard neoadjuvant treatment in patients with high-risk HER2-positive early breast cancer, a phase 3 trial suggests.
In the IMpassion050 trial, adding atezolizumab to neoadjuvant dose-dense doxorubicin/cyclophosphamide, paclitaxel, and pertuzumab-trastuzumab (PH) did not increase the rate of pathological complete response (pCR).
Researchers reported these results in the Journal of Clinical Oncology.
The phase 3 IMpassion050 trial (ClinicalTrials.gov identifier: NCT03726879) enrolled 454 patients with high-risk HER2-positive early breast cancer.
Patients were randomly assigned to receive neoadjuvant atezolizumab (n=226) or placebo (n=228), each in combination with dose-dense doxorubicin/cyclophosphamide, paclitaxel, and PH. After surgery, patients could continue atezolizumab/placebo and PH. Patients who had residual disease at surgery could switch to ado-trastuzumab emtansine.
At baseline, the median age in both treatment arms was 50 years, all but 1 patient in each arm was a woman, and a majority of patients in both arms were White. About half of patients in each arm had hormone receptor-positive disease, about half had PD-L1-negative tumors, and a majority had wild-type PIK3CA.
The co-primary endpoints were pCR in the intent-to-treat (ITT) population and in the PD-L1-positive population. In the ITT population, the pCR rate was 62.7% with placebo and 62.4% with atezolizumab (P =.9551). Among patients with PD-L1-positive tumors, the pCR rate was 72.5% with placebo and 64.2% with atezolizumab (P =.1846).
“The lack of pCR improvement with atezolizumab in IMpassion050 is surprising, given the expected greater benefit of cancer immunotherapy in EBC [early breast cancer] compared with the advanced setting, because of a lower tumor burden, reduced immune escape mechanisms, and a more efficient immune system in patients with EBC,” the researchers wrote.
The median event-free survival (EFS) was not estimable in either treatment arm. There were 7 EFS events in the placebo arm and 12 in the atezolizumab arm (P =.2084)
In the neoadjuvant phase, 100% of patients in both arms had treatment-related adverse events (TRAEs). In the adjuvant phase, the rate of TRAEs was 67.4% in the placebo arm and 75.5% in the atezolizumab arm.
In the neoadjuvant phase, the rate of grade 3-4 TRAEs was 42.2% in the placebo arm and 47.3% in the atezolizumab arm. In the adjuvant phase, the rate of grade 3-4 TRAEs was 9.8% and 13.4%, respectively.
There were 2 fatal TRAEs in the atezolizumab arm and none in the placebo arm.
Disclosures: This research was supported by F. Hoffman-La Roche, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Huober J, Barrios CH, Niikura N, et al. Atezolizumab with neoadjuvant anti-human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2-positive early breast cancer: Primary results of the randomized phase III IMpassion050 trial. J Clin Oncol. Published online June 28, 2022. doi:10.1200/JCO.21.02772