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Atezolizumab plus chemotherapy approved for triple-negative breast cancer, small cell lung cancer
The FDA granted accelerated approval to atezolizumab plus chemotherapy for the treatment of adults with PD-L1-positive, unresectable, locally advanced or metastatic triple-negative breast cancer.
Atezolizumab (Tecentriq, Genentech/Roche) — a monoclonal antibody that binds with PD-L1 to block its interactions with PD-1 and B7.1 receptors — also received approval for use with carboplatin and etoposide for the first-line treatment of patients with extensive-stage small cell lung cancer.
Triple-negative breast cancer
The approval of atezolizumab plus nab-paclitaxel (Abraxane, Celgene) — which applies to patients whose tumors express PD-L1 on an FDA-approved test — is based on PFS data from the ongoing randomized phase 3 IMpassion130 study; ongoing approval may depend upon substantiation and description of clinical benefit in confirmatory trials.
The multicenter, double-blind IMpassion130 study is evaluating the safety and efficacy of atezolizumab and nab-paclitaxel vs. placebo and nab-paclitaxel among 902 patients with unresectable, locally advanced or metastatic triple-negative breast cancer who had no previous systemic therapy for metastatic disease. PFS among the intention-to-treat population and patients with PD-L1-positive disease and OS in the intention-to-treat population served as the co-primary endpoints.
Results showed significantly longer median PFS with the atezolizumab regimen vs. nab-paclitaxel alone (7.4 months vs. 4.8 months; HR = 0.6, 95% CI, 0.48-0.77).
Data on OS were immature, with 43% of events in the entire intention-to-treat population. Further data will be reported to the FDA and presented at a future medical meeting.The combination demonstrated a safety profile consistent with the known safety of each drug, and the combination yielded no new safety signals.
The most common grade 3 to grade 4 adverse events among 2% or more of patients included low white blood cells, tingling or numbness in the hands and feet, reduced neutrophil count, fatigue, low red blood cells, low blood potassium level, pneumonia and increased blood level of aspartate transaminase.
The most common adverse events among 20% or more of patients were hair loss, fatigue, numbness in the hands and feet, nausea, diarrhea, low red blood cells, constipation, cough, headache, low white blood cells, diminished appetite and vomiting.
“The Tecentriq 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,” Hayley Dinerman, executive director of the Triple Negative Breast Cancer Foundation, said in a press release. “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.”
Small cell lung cancer
Atezolizumab plus chemotherapy is the first new frontline treatment option approved for extensive-stage small cell lung cancer in more than 20 years.
“Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat,” Sandra Horning, MD, chief medical officer and head of global product development at Roche, said in a press release. “Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy.”
The approval was based, in part, on data from the multicenter, double-blind phase 3 IMpower133 study. Researchers randomly assigned 403 treatment-naive patients with extensive-stage small cell lung cancer 1:1 to 1,200 mg atezolizumab or placebo on day 1 with carboplatin (area under the curve 5 mg/mL/min on day 1) and etoposide (100 mg/m2 IV on days 1, 2 and 3 of each 21-day cycle for four cycles). Following the first four cycles, patients received 1,200 mg atezolizumab or placebo once every 3 weeks until progression or unacceptable toxicity.
Results showed the combination of atezolizumab and chemotherapy significantly extended median OS in the intention-to-treat population compared with chemotherapy alone (12.3 months vs. 10.3 months; HR = 0.7; 95% CI, 0.54-0.91).
The combination also conferred longer median PFS (5.2 months vs. 4.3 months; HR = 0.77; 95% CI, 0.62-0.96).
Serious adverse events occurred among 37% of patients receiving atezolizumab plus chemotherapy and 35% of patients receiving chemotherapy alone. The most common adverse events that occurred among at least 20% of patients who received atezolizumab included fatigue/asthenia (39%), nausea (38%), alopecia (37%), constipation (26%), decreased appetite (27%) and vomiting (20%).