Adding atezolizumab to standard of care treatment for human epidermal growth factor receptor 2 (HER2) positive early breast cancer does not improve pathologic response outcomes

1. The pathologic response rate was similar in the atezolizumab treatment group as compared to placebo.

2. There were more frequent serious adverse events in the atezolizumab group compared to placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: In roughly 15-20% of breast carcinomas, human epidermal growth factor receptor 2 (HER2) is overexpressed and results in an aggressive cancer with poor outcomes. Because of their targeted effects on HER2, pertuzumab and trastuzumab (PH) therapy in combination with chemotherapy is the standard of care for HER2-positive early breast cancer (EBC). This study aimed to determine the effect of combining atezolizumab, a programmed cell death-ligand 1 (PD-L1) inhibitor, with the standard of care treatment for HER2-positive EBC on outcomes of pathologic complete response (pCR) rate, event-free survival (EFS), and safety. The pCR rates for the azetolizumab group was 62.4% and for the placebo group it was 62.7%. In the PD-L1-positive subgroup, pCR rates were 72.5% for placebo and 64.2% with atezolizumab. In the PD-L1-negative subgroup, pCR rates were 53.8% for placebo and 60.7% for atezolizumab. There were more patients in the azetolizumab group that had an EFS event than in the placebo group (5.3% compared to 3.1%, respectively). Neither group had an estimable median EFS. There were a greater frequency of serious adverse events (AEs) in the azetolizumab group compared to placebo. There were 2 fatal AEs that were attributable to azetolizumab treatment (alveolitis and septic shock). Limitations to this study include small sample size in some of the subgroups as well as limited power of the study to determine long-term outcomes. Overall, the standard of care treatment for HER2-positive EBC is not improved by the addition of azetolizumab.

Click to read the study in The Journal of Clinical Oncology

Relevant Reading: A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: Clinical results and biomarker analysis of GeparNuevo study.

In-Depth [randomized controlled trial]: This international, multi-centre, randomized, controlled trial included 454 adult patients assigned in a 1:1 fashion to receive neoadjuvant dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and PH (ddAC-PacPH) with either atezolizumab (n = 226) or placebo (n = 228). There were 109 patients in each of the placebo and treatment group with PD-L1-positive tumours There were 119 and 117 patients in the placebo and treatment group, respectively, with PD-L1-negative tumours. The pCR rates for the azetolizumab group was 62.4% and for the placebo group it was 62.7% (a difference of -0.33%; 95% confidence interval (CI), -9.23 to 8.57%). The pCR rates were 72.5% for placebo and 64.2% with atezolizumab in the PD-L1-positive subgroup (a difference of -8.26%; 95% confidence interval (CI), -20.56 to 4.04%). pCR rates were 53.8% for placebo and 60.7% for atezolizumab in the PD-L1-negative subgroup (a difference of 6.90%; 95% CI, -5.29 to 19.49%). For EFS, 3.1% in the placebo group and 5.3% of the azetolizumab group experienced an event, with neither group having an estimable median EFS. AEs of grade 3 or 4 were more common in the treatment group. All five of the grade 5 AEs that occurred during the trial were in the azetolizumab group. Two fatal AEs were found to be attributable to treatment with azetolizumab.

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