Add-on atezolizumab of no benefit in HER2-positive breast cancer with brain metastases

Using atezolizumab in addition to pertuzumab plus high-dose trastuzumab does not appear to improve central nervous system (CNS) responses in HER2-positive breast cancer patients with brain metastases, according to the results of a single-arm phase II study.

The study included 19 patients (median age 50 years, 89.5 percent White) with HER2-positive breast cancer brain metastases. These patients received treatment with atezolizumab 1,200 mg every 3 weeks, pertuzumab (loading dosage 840 mg, then 420 mg every 3 weeks), and high-dose trastuzumab (6 mg/kg weekly for 24 weeks, then 6 mg/kg every 3 weeks), administered intravenously.  

The primary endpoint of CNS overall response rate was assessed per Response Assessment in Neuro-Oncology Brain Metastases criteria. Key secondary endpoints included clinical benefit rate, overall survival, and safety and tolerability of the treatment combination.

Disease was between stage II-IV at diagnosis, and most patients (63.2 percent) had ECOG PS 0 at baseline. The disease-free interval was >2 years for 47.4 percent of patients.

The study was terminated early due to the failure to meet the prespecified efficacy threshold. Of the patients, only two showed a confirmed intracranial partial response, yielding a CNS overall response rate of 10.5 percent (90 percent confidence interval, 1.9–29.6). The clinical benefit rate was 42.1 percent at 18 weeks and 31.6 percent at 24 weeks.

Dose was delayed or held for seven patients (36.8 percent), with the most frequent any-grade adverse events being diarrhoea (26.3 percent) and fatigue (26.3 percent).