The FDA has approved atezolizumab (Tecentriq®, Genentech, Inc.) in combination with nab-paclitaxel as a first-line treatment for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express programmed death-ligand 1 (PD-L1). This is the first FDA approval of an immune checkpoint inhibitor for any type of breast cancer. It is also a substantial development for patients with TNBC, a highly aggressive subtype that lacks many of the targeted therapies that can be used in other types of breast cancer.
"The [atezolizumab] 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," commented Hayley Dinerman, Executive Director of the Triple Negative Breast Cancer Foundation. "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."
The approval was based on the multicenter, international, double-blinded, phase 3 IMpassion130 trial (NCT02425891), for which 902 patients with previously untreated metastatic TNBC were randomized in a 1:1 ratio to receive either atezolizumab 840 mg or placebo intravenously on days 1 and 15 of every 28-day cycle in combination with nab-paclitaxel until disease progression or unacceptable toxicity. Patients were followed for a median of 12.9 months. The study's primary end points were progression-free survival, both in the intention-to-treat (ITT) population and in the PD-L1–positive subgroup, and overall survival, both in the ITT population and also in the PD-L1–positive subgroup if overall survival was statistically significant in the ITT population.
In combination with nab-paclitaxel, atezolizumab improved median progression-free survival compared with placebo in the ITT population (7.2 vs 5.5 months) and in patients with PD-L1–positive tumors (7.5 vs 5.0 months). Atezolizumab also increased median overall survival, both in the ITT population (21.3 vs 17.6 months) and in patients with PD-L1–positive tumors (25.0 vs 15.5 months).
Adverse events leading to discontinuation of any agent occurred in 15.9% of patients in the atezolizumab/nab-paclitaxel group, compared with 8.2% of patients receiving placebo/nab-paclitaxel. Adverse reactions occurring in at least 20% of patients receiving atezolizumab/nab-paclitaxel included alopecia, peripheral neuropathies, fatigue, nausea, diarrhea, anemia, constipation, cough, headache, neutropenia, vomiting, and decreased appetite.
In addition to the atezolizumab/nab-paclitaxel approval, the FDA approved the VENTANA PD-L1 (SP142) assay (Roche Diagnostics) as a companion device for selecting atezolizumab-eligible patients with TNBC.
The atezolizumab/nab-paclitaxel combination has been granted accelerated approval based on progression-free survival. Continued approval may depend on verification and description of clinical benefit in one or more confirmatory trials.
The recommended dosage for patients with TNBC and PD-L1–positive tumors is 840 mg atezolizumab administered intravenously over 60 minutes, followed by 100 mg/m2 nab-paclitaxel. Atezolizumab is administered on days 1 and 15 of each 28-day cycle, with nab-paclitaxel administered on days 1, 8, and 15, until disease progression or unacceptable toxicity.
For More Information
Clinicaltrials.gov (2019). A study of atezolizumab in combination with nab-paclitaxel compared with placebo with nab-paclitaxel for participants with previously untreated metastatic triple-negative breast cancer (IMpassion130). NLM identifier: NCT02425891.
Schmid P, Adams S, Rugo HS, et al (2018). Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 379(22):2108-2121. DOI:10.1056/NEJMoa1809615
Image credit: Wei Qian. Courtesy of the National Cancer Institute, University of Pittsburgh Cancer Institute