A new phase II study recently published on Clinical Cancer Research shows that adding atezolizumab to pertuzumab plus high-dose trastuzumab does not improve central nervous system responses in HER2+ breast cancer patients with brain metastases.

In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate in the central nervous system in patients with brain metastases. Authors thus enrolled in a single-arm, multi-center, phase II trial 19 patients with HER2-positive breast cancer brain metastases to assess whether the addition of atezolizumab to this regimen would produce further improvements in central nervous system response. Results showed that only two patients had a confirmed intracranial partial response (objective response rate of 10.5%); the clinical benefit rate was 42.1% at 18 weeks and 31.6% at 24 weeks. The study did not meet the prespecified efficacy threshold and was terminated early. As authors conclude «The addition of atezolizumab to pertuzumab and high-dose trastuzumab did not produce clear central nervous system benefit in patients with HER2+ breast cancer with brain metastases beyond that which would have been expected with pertuzumab and high-dose trastuzumab alone. However, the study was limited by the low proportion of patients with PD-L1 tumors and by the single-arm design, and does not rule out the potential for immunotherapy to result in clinical benefit in biomarker-enriched populations. Further studies of immunotherapy plus anti-HER2 therapy should include distinct agents other than PD-1/PD-L1 inhibitors».