The international, double-blind, phase lll IMpassion031 trial randomly assigned 333 patients with early, treatment-naive TNBC to receive atezolizumab or placebo. Of the eligible trial participants, 165 patients were randomly assigned to receive intravenous atezolizumab at 840 mg every 2 weeks plus nab-paclitaxel at 125 mg/m2 every week for 12 weeks, followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, followed by surgery. The remaining patients randomly were assigned to receive placebo plus the chemotherapy regimen, which was also followed by surgery.
Patients in the experimental arm received atezolizumab for an additional 11 doses, whereas patients in the placebo arm were observed. Patients were stratified by stage and PD-L1 positivity. The coprimary endpoints were pCR in the intention-to-treat (ITT) and PD-L1–positive (tumor-infiltrating immune cells ≥1%) polulations. Secondary endpoints were event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) in the ITT and PD-L1–positive populations; however, at press time, OS data were not yet mature.
The baseline characteristics of trial participants were comparable between arms, with an average patient age of 51 years; 63% of patients were Caucasian, 26% were Asian, and 7% were African American. Most patients had stage II disease (77%) and 54% had PD-L1–positive disease. The study results reported that after an average follow-up of around 20 months, the pCR in the atezolizumab arm was considerably greater at 57.6% compared with 41.1% in the placebo arm (P =.0044). The benefit was observed regardless of PD-L1–positivity, as patients with PD-L–negative disease in the atezolizumab arm demonstrated a pCR of 47.7% compared with 34.4% in the placebo arm (P =.021), which did not cross the prespecified boundary.
With regard to adverse drug reactions (ADRs), the majority of patients (99.4%) in the atezolizumab arm experienced at least one adverse event. Furthermore, 100% of the placebo arm experienced at least one adverse event. Treatment related grade 3-4 adverse events were reported in 56.7% of patients who received the atezolizumab-chemotherapy regimen and 53.3% of patients who received the placebo regimen. The most common ADRs in the neoadjuvant phase reported in both the atezolizumab and placebo arm included, but were not limited to, alopecia (75% vs. 77.2%, respectively), nausea (64.6% vs. 67.1%, respectively) and diarrhea (41.5% vs. 44.3%, respectively).
The researchers noted that there seems to be a positive trend for atezolizumab plus the chemotherapy regimen in improving EFS, DFS, and OS, though, further research is ongoing. The researchers concluded that in patients with early stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy considerably improved pathological complete response rates with an acceptable safety profile.
At the 2020 ESMO meeting, presenter Nadia Harbeck, MD, stated, “This new combination therapy may offer an improved curative treatment option for this patient population with a high unmet medical need.” Dr Harbeck also concluded, “Atezolizumab plus chemotherapy resulted in a statistically significant and clinically meaningful plus 16.5% increase in pCR rate vs placebo plus chemotherapy.”
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