Study Finds No Benefit to Adding Checkpoint Inhibitors to Anti-HER2 Breast Cancer Therapy


The trial, in phase 3, is the first to report data comparing a neoadjuvant anti-HER2 based regimen with or without the anti-PD-L1 antibody, atezolimumab, in patients with high-risk, HER2-positive early breast cancer.

A primary analysis of the IMpassion 050 trial found that adding an immune checkpoint inhibitor to anti-human epidermal growth factor receptor 2 (HER2) treatment in breast cancer does not improve pathological complete response (pCR), according to a virtual plenary session at the European Society for Medical Oncology conference.

The trial, in phase 3, is the first to report data comparing a neoadjuvant anti-HER2 based regimen with or without the anti-PD-L1 antibody, atezolimumab, in patients with high-risk, HER2-positive early breast cancer, according to a press release.

Although antibody therapy may increase essential, adaptive immunity and activate cellular cytotoxicity, the study authors noted that there is evidence that a treatment combination including a checkpoint inhibitor may further enhance the immune response. The objective of the trial was to evaluate the efficacy and safety of neoadjuvant atezolizumab versus placebo in patients receiving dose-dense anthracycline and taxane-based chemotherapy as a successive treatment in combination with the antibodies pertuzumab and trastuzumab.

Participants included 454 patients with high-risk HER2-positive early breast cancer, meaning they had a primary breast tumor size of less than 2 cm and pathologic confirmation of nodal involvement. The patients were randomly allocated in a 1:1 ratio to the 2 treatment arms and received 6 months of neoadjuvant therapy. Further, the patients resumed their allocated treatment with atezolizumab versus placebo following surgery. Those with pCR continued pertuzumab and trastuzumab, whereas those with residual disease could switch to trastuzumab emtansine (T-DM1).

The trial was stopped early when an Independent Data Monitoring Committee considered an unfavorable benefit-risk profile with the intervention. However, the data were analyzed at an earlier stage, with 3 patients still waiting to go through surgery.

The pCR was achieved by 62.4% of the atezolizumab arm and 62.7% of the placebo arm in the intention to treat (ITT) population. Furthermore, in the PD-L1-positive population, pCR was achieved by 64.2% of the atezolizumab arm and 72.5% of the placebo arm. There were higher rates of grade 3 and 4 adverse events (AEs) and serious AEs in the neoadjuvant phase with atezolimumab versus placebo, respectively. Four patients in the atezolizumab group died compared to zero patients in the placebo group during neoadjuvant treatment, according to the study authors.

“Overall, the safety profile was consistent with other combination studies with atezolizumab, with no new side-effects,” said lead author Jens Huober, professor of gynecologic oncology at the Breast Centre St. Gallen, Switzerland, in the press release. “It is important to note that this was a selected population of high-risk HER2-positive patients to justify the potential toxicity of the additional drug and because patients with HER2-positive, node negative, smaller tumors do well with standard treatment.”

Huober also mentioned that the additional immunotherapy in this setting did not enhance the pCR rate in the overall population or in any subgroup.

“However, what counts for patients are EFS and overall survival, which were secondary endpoints and we need longer follow-up for those results. In addition, there is some evidence in triple negative breast cancer that pCR may not be the best endpoint for measuring the efficacy of immunotherapy,” Huober said.

Carmen Criscitiello, MD, said the findings of this study should be examined carefully given the setting.

“Toxicity is more or less in line with what has been reported with similar combinations in other settings. There is a need to investigate if there is any link between atezolizumab and the treatment-related deaths, although- except alveolitis- they were not typical immune-related side-effects,” Criscitiello said in the press release. “In the curative setting we should be even more conservative and cautious when we look at the toxicity that may be induced by a new treatment. So far, this combination has not demonstrated an improvement in pCR rate, so the balance between risk and benefit should be carefully monitored before considering this therapeutic strategy.”


Adding checkpoint inhibition to anti-HER2 breast cancer therapy brings no benefit. ESMO 2021. June 17, 2021. Accessed June 18, 2021.

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