The FDA granted accelerated approval to atezolizumab (Tecentriq) for advanced triple-negative breast cancer (TNBC), marking the first immunotherapy with a breast cancer indication.
The PD-L1 checkpoint inhibitor was approved in combination with nab-paclitaxel (Abraxane) for metastatic or locally advanced, unresectable TNBC, according to the , manufacturer of atezolizumab.
Results of the phase III study that led to Friday's approval, IMpassion30, were presented last fall at the European Society for Medical Oncology (ESMO) congress. The trial randomized over 900 TNBC patients to the combination of atezolizumab plus nab-paclitaxel or nab-paclitaxel plus placebo, 369 of whom had PD-L1-positive tumors (≥1% expression in tumor infiltrating cells).
In the PD-L1-positive patients, progression-free survival (PFS) in the atezolizumab arm was 7.4 months compared with 4.8 months in the placebo arm (HR 0.60, 95% CI 0.48-0.77, P<0.0001). Overall survival (OS) data were not yet mature in the intent-to-treat population, but in data from ESMO, an OS advantage in the PD-L1 group was already seen in favor of the combination arm (HR 0.62, 95% CI 0.45-0.86).
At the meeting, Marlene Kok, MD, of The Netherlands Cancer Institute in Amsterdam, said the trial results "will probably change the treatment landscape for our metastatic triple-negative breast cancer patients."
Response rates in the PD-L1-positive patients were 58.9% with atezolizumab and 42.6% with placebo. Median duration was 8.5 versus 5.5 months, respectively.
"This is tremendously exciting news," said Amy Tiersten, MD, of the Tisch Cancer Institute at Mount Sinai in New York City, in an email following the approval announcement. "I am thrilled to be able to offer this revolutionary therapy to our patients!"
Under the conditions of accelerated approval, full approval will rest upon confirmatory trial data.
Safety in IMpassion30 was similar to other atezolizumab trials, with the most common (≥20%) adverse events (AEs) including alopecia, constipation, cough, headache, fatigue, nausea and vomiting, decreased appetite, diarrhea, low red and white blood cell counts, and neuropathy.
The most common grade 3/4 AEs (≥2%) include low red and white blood cell counts, decreased neutrophil counts, fatigue, increased aspartate transaminase levels, low blood potassium levels, neuropathy, and pneumonia.