As reported in The Lancet by Elizabeth A. Mittendorf, MD, and colleagues, results from the phase III IMpassion031 trial showed improved pathologic complete response rates with the addition of atezolizumab to sequential nab-paclitaxel and anthracycline-based neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer.

Elizabeth A. Mittendorf, MD

Study Details

In the double-blind trial, 333 patients from sites in 13 countries with previously untreated stage II or III disease were randomly assigned between July 2017 and September 2019 to receive neoadjuvant atezolizumab plus chemotherapy (n = 165) or placebo plus chemotherapy. Atezolizumab was given at 840 mg every 2 weeks. Chemotherapy consisted of 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. The co-primary endpoints were pathologic complete response rates in the intent-to-treat population and in the population of patients with PD-L1–positive tumors (PD-L1–expressing tumor infiltrating immune cells covering ≥ 1% of tumor area). Overall, 47% of patients in the atezolizumab group and 45% of those in the control group had PD-L1–positive tumors.

Pathologic Complete Response Rates

In the intent-to-treat population, pathologic complete response was achieved in 95 patients (58%) in the atezolizumab group vs 69 patients (41%) in the control group (rate difference = 17%, 95% confidence interval [CI] = 6%­–27%, P = .0044, crossing the significance boundary of .0184).

In the PD-L1–positive population, pathologic complete response was achieved in 53 (69%) of 77 patients in the atezolizumab group vs 37 (49%) of 75 patients in the control group (rate difference = 20%, 95% CI = 4%–35%, P = .021, crossing the significance boundary of .0184).

In the PD-L1–negative population, pathologic complete response was achieved 42 patients (48%) in the atezolizumab group vs 32 patients (34%) in the control group (rate difference = 13%, 95% CI = −1%–28%).

Adverse Events

Grade 3 or 4 adverse events occurred in 63% of those in the atezolizumab group vs 60% of the control group, with those occurring at an incidence ≥ 2% greater in the atezolizumab group being leukopenia (9% vs 5%), increased aspartate aminotransferase (4% vs 2%), and pneumonia (3% vs 0%). Serious adverse events occurred in 30% vs 18% of patients, with the most common in both groups being febrile neutropenia (10% vs 8%), pneumonia (3% vs 1%), and pyrexia (2% vs 0%). Adverse events of special interest of any grade occurred in 70% vs 60% of patients, with the most common being rash (49% vs 49%), hypothyroidism (7% vs 1%), and infusion-related reactions (10% vs 7%).

The investigators concluded, “In patients with early-stage triple-negative breast cancer, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile.”

Dr. Mittendorf, of Dana-Farber/Brigham and Women’s Cancer Center, is the corresponding author for The Lancet article.

Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. For full disclosures of the study authors, visit thelancet.com.