Atezolizumab Receives FDA Approval as First Immune Therapy for PD-L1-Positive Triple-Negative Breast Cancer

Recently, the U.S. Food and Drug Administration (FDA) granted priority review for Genentech’s PD-L1 monoclonal antibody atezolizumab (Atezolizumab), in combination with chemotherapy, as a first-line treatment for unresectable locally advanced or metastatic PD-L1-positive triple-negative breast cancer (TNBC). This marks the first approved immunotherapy for triple-negative breast cancer.

It should be specifically noted that this therapy requires patients’ tumors to be PD-L1 positive, and PD-L1 expression must be assessed using the FDA-approved companion diagnostic test, VENTANA PD-L1 (SP142).

Triple-Negative Breast Cancer (TNBC) is a distinct subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC accounts for approximately 15% of all breast cancer cases. Due to the lack of targets for endocrine therapy and anti-HER2 treatments, first-line standard regimens consist of single-agent taxane or anthracycline chemotherapy. Currently, there are no targeted therapies specifically approved for TNBC. However, researchers have discovered that TNBC can express PD-L1, which impairs the ability of immune cells to recognize tumors. This suggests that PD-L1 inhibitors may be effective in treating TNBC. According to statistics from the U.S. Breast Cancer Foundation, approximately one-fifth of patients with triple-negative breast cancer express PD-L1. Consequently, immunotherapies for triple-negative breast cancer have emerged.

It is understood that the approval of atezolizumab was based on a trial named IMpassion130, which enrolled 902 patients with unresectable locally advanced or metastatic triple-negative breast cancer who had not previously received chemotherapy. These patients were randomly assigned to two groups: one group received atezolizumab plus chemotherapy, and the other group received placebo plus chemotherapy.

The final results showed that atezolizumab significantly reduced the risk of disease progression or death. In the intent-to-treat (ITT) population, atezolizumab significantly reduced the risk of disease progression or death (progression-free survival; PFS) compared with placebo (median PFS = 7.2 vs. 5.5 months; hazard ratio [HR] = 0.80, 95% confidence interval [CI], 0.69–0.92; P = .0025).

Meanwhile, atezolizumab also improved median overall survival (OS), but did not reach statistical significance in the interim analysis (21.3 vs. 17.6 months; HR = 0.84, 95% CI, 0.69-1.02, P = .0840).

In terms of adverse effects, the most common side effects in the Atezolizumab group included alopecia, peripheral neuropathy, fatigue, nausea, diarrhea, anemia, constipation, cough, headache, and decreased appetite.

According to the latest news, an application for Atezolizumab has also been submitted in China, with lung cancer as the first indication sought. Chinese patients are expected to have access to this drug in the second half of the year.