On March 8, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the combination of atezolizumab (Tecentriq®, Genentech) and nab-paclitaxel chemotherapy for the first-line treatment of patients with PD-L1-positive triple-negative breast cancer (TNBC) that is either unresectable (inoperable) or metastatic (has spread to other parts of the body).
This marks the first approval of a checkpoint immunotherapy—in this case, the PD-L1-targeting atezolizumab—for any type of breast cancer, and represents an especially important advance for patients with the triple-negative subtype (TNBC), which, although less common, is the most aggressive form of breast cancer. In patients with metastatic TNBC, the median survival is a little over one year, meaning that, historically, only half of patients survive that long after diagnosis. According to the National Breast Cancer Foundation, roughly 10-20% of all breast cancers are characterized as TNBC, meaning that they express neither the HER2 receptor nor receptors for the hormones estrogen and progesterone and therefore do not respond to treatments that target these receptors.
This important approval was based on results from the phase III IMpassion130 clinical trial, in which 902 patients with advanced TNBC were enrolled to receive either the immunotherapy-chemotherapy combination or chemotherapy alone. In the patients whose tumors expressed the PD-L1 immune checkpoint, combination treatment was associated with a “clinically meaningful improvement” in overall survival—25 months versus 15.5 months—and also reduced the risk of disease progression or death by roughly 40% compared to those who were treated with chemotherapy alone. Of the patients treated with the combination, 54% survived at least two years compared to only 37% of chemotherapy-treated patients.
Additionally, the combination led to superior progression-free survival (median of 7.4 months versus 4.8 months) and response rates (59% versus 43%) in the PD-L1-positive patients. Side effects occurred at similar rates between the two groups, with 23% of combination-treated patients and 18% of chemotherapy-treated patients reporting serious adverse events, with the most common being hypothyroidism, which occurred in 17% of combination-treated patients
“[This] FDA approval…is an important treatment advance for people with PD-L1–positive, metastatic triple-negative breast cancer, a disease with high unmet medical need,” according to Sandra Horning, M.D., Genentech’s chief medical officer and head of global product development. “This Tecentriq combination is the first cancer immunotherapy regimen to be approved in breast cancer, representing a meaningful step forward in the understanding of this disease.”
Hayley Dinerman, the executive director of the Triple Negative Breast Cancer Foundation, added that this “regimen is an exciting new treatment option for certain people living with metastatic triple-negative breast cancer, a difficult-to-treat form of the disease. Chemotherapy alone has been the mainstay of treatment for many years, so it’s encouraging to now have an immunotherapy combination available for people with PD-L1-positive disease.”
For more information on the changing landscape of breast cancer treatment, read the CRI Clinical Accelerator team’s newly published article in The Lancet Oncology “Immunotherapy and targeted therapy combinations in metastatic breast cancer.”