medwireNews: Adding atezolizumab to neoadjuvant dual-HER2 blockade plus chemotherapy does not boost pathologic complete response (pCR) rates in people with high-risk, HER2-positive, early breast cancer, find the IMpassion050 investigators.
The trial’s independent data monitoring committee recommended early termination of atezolizumab treatment “due to an unfavorable benefit–risk profile,” said presenting author Jens Huober (Breast Center St Gallen, Switzerland) at the ESMO Virtual Plenary, noting that chemotherapy in combination with trastuzumab plus pertuzumab remains the current standard of care in this setting.
He continued: “Further data are needed to clarify the role of cancer immunotherapies in HER2-positive breast cancer.”
“Atezolizumab may yet play an important role, particularly in other combination studies with long-term primary endpoints such as overall survival and disease-free survival that may allow a better measure of its immune-mediated anti-tumor effects over longer time.”
In the phase 3 study, 454 patients with clinical stage T2–T4, N1–N3, M0 disease were randomly assigned to receive atezolizumab or placebo alongside four cycles of neoadjuvant dose-dense doxorubicin plus cyclophosphamide. The allotted study treatment was then continued during the subsequent four cycles of paclitaxel plus trastuzumab and pertuzumab, and then with dual-HER2 blockade after surgery for up to 52 weeks.
There were no significant differences between the atezolizumab and placebo groups in terms of the co-primary endpoints of pCR in the intention-to-treat (ITT) and PD-L1-positive populations, at rates of 62.4% versus 62.7%, and 64.2% versus 72.5%, respectively.
The secondary endpoint of pCR in PD-L1-negative patients was likewise comparable between atezolizumab- and placebo-treated patients (60.7 vs 53.8%).
And the event-free survival curves in the ITT population were superimposed at the time of analysis, indicating no significant difference between the treatment groups, reported Huober.
He pointed out, however, that “the median follow-up is quite short and we have to wait for a longer time to draw definite conclusions with regard to a long-term outcome like event-free survival or overall survival.”
In terms of the safety profile, there was a higher incidence in the atezolizumab than placebo arm of grade 3–4 adverse events (AEs; 51.8 vs 43.6% in the neoadjuvant phase, 24.1 vs 16.7% in the adjuvant phase) and serious AEs (19.5 vs 13.3% in the neoadjuvant phase, 11.1 vs 8.4% in the adjuvant phase).
There were also more AE-related deaths among atezolizumab- versus placebo-treated participants (four vs none in the neoadjuvant phase, one vs none in the adjuvant phase), but the presenter pointed out that “all events were confounded by comorbidities and concurrent events.”
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