Adding an immune checkpoint inhibitor to anti-HER2 treatment in breast cancer does not improve pathological complete response (pCR), according to the primary analysis of the IMpassion050 trial presented today during the ESMO Virtual Plenary. The phase III trial is the first to report data comparing a neoadjuvant anti-HER2 based regimen with or without the anti-PD-L1 antibody atezolizumab in patients with high-risk, HER2-positive early breast cancer. The standard treatment for high-risk, HER2-positive early breast cancer is dual anti-HER2 blockade plus chemotherapy. While antibody therapy may enhance innate and adaptive immunity and activate cellular cytotoxicity, there is evidence that combination with a checkpoint inhibitor may further enhance the immune response. IMpassion050 evaluated the efficacy and safety of neoadjuvant atezolizumab versus placebo in patients receiving dose-dense anthracycline and taxane-based chemotherapy as a sequential treatment in combination with the antibodies pertuzumab and trastuzumab.

The trial enrolled 454 patients with high-risk HER2-positive early breast cancer, meaning they had a primary breast tumor size of >2 cm, and pathologic confirmation of nodal involvement. Patients were randomly allocated in a 1:1 ratio to the two treatment arms and received six months of neoadjuvant therapy. Following surgery, patients resumed their allocated treatment with atezolizumab versus placebo. Patients with pCR continued pertuzumab and trastuzumab while those with residual disease could switch to trastuzumab emtansine (T-DM1).

The co-primary endpoints were pCR in the intention to treat (ITT) and PD-L1 positive populations. Event-free survival (EFS), overall survival and safety were secondary endpoints. The trial was stopped prematurely when the Independent Data Monitoring Committee judged that there was an unfavorable benefit-risk profile with the intervention. The data were analyzed early, with three patients still to undergo surgery.

Regards

John
Editorial Assistant
Journal of Medical and Surgical Pathology