The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of the frontline combination of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) for the treatment of adult patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer.
Sandra Horning, MD
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of the frontline combination of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) for the treatment of adult patients with unresectable locally advanced or metastatic PD-L1—positive triple-negative breast cancer (TNBC).
The CHMP recommendation, which is for patients with a PD-L1 expression level ≥1%, is based on data from the phase III IMpassion130 trial, in which the addition of the PD-L1 inhibitor atezolizumab to nab-paclitaxel reduced the risk of progression or death by 38% compared with nab-paclitaxel alone in this patient population. The European Commission will now make its final decision on approval of the regimen.
“This CHMP recommendation marks a breakthrough in the treatment of triple-negative breast cancer, an aggressive type of breast cancer with high unmet medical need,” Sandra Horning, MD, Roche’s chief medical officer and head of global product development, said in a statement. “With today’s announcement, we hope that people living with PD-L1—positive metastatic triple-negative breast cancer in Europe will soon have a new treatment option with the Tecentriq combination.”
The double-blind IMpassion130 study evaluated the efficacy and safety of the PD-L1 inhibitor plus chemotherapy versus nab-paclitaxel alone in treatment-naïve patients with metastatic TNBC. Patients were randomized 1:1 to receive nab-paclitaxel at 100 mg/m2 intravenously on days 1, 8, and 15 of the 28-day cycle with atezolizumab at 840 mg intravenously (n = 451) on days 1 and 15 of a 28-day cycle or with placebo (n = 451). Treatment was given until disease progression or unacceptable toxicity.
The coprimary endpoints were progression-free survival (PFS) and overall survival (OS) in both the intent-to-treat (ITT) and PD-L1—positive populations; secondary endpoints were overall response rate, duration of response, and safety. Patients were stratified by prior taxane use, liver metastases, and PD-L1 expression, which was defined as at least 1% on tumor-infiltrating immune cells to be positive.
Results of the primary PFS analysis in the PD-L1—positive population demonstrated a clinically meaningful median PFS of 7.5 months with atezolizumab/nab-paclitaxel and 5 months with chemotherapy (HR, 0.62; 95% CI, 0.49-0.78; P <.0001).1,2 Moreover, the 1-year PFS rates were 29% (95% CI, 22%-36%) and 16% (95% CI, 11%-22%) with atezolizumab/nab-paclitaxel and nab-paclitaxel, respectively.
In the ITT population, the median PFS with atezolizumab/nab-paclitaxel and nab-paclitaxel was 7.2 months (95% CI, 5.6-7.5) and 5.5 months (95% CI, 5.3-5.6), respectively (HR, 0.80; 95% CI, 0.69-0.92; P = .0025). Moreover, the 1-year PFS rates were 24% (95% CI, 20%-28%) in the combination arm and 18% (95% CI, 14%-21%) in the nab-paclitaxel arm.
An interim OS analysis of the PD-L1—positive population showed a clinically meaningful improvement with added atezolizumab at 25.0 months versus nab-paclitaxel alone at 18.0 months (HR, 0.71; 95% CI, 0.54-0.93). Two-year OS rates were 54% and 37% in the immunotherapy/chemotherapy and chemotherapy arms, respectively. In the ITT population, the P value for OS was .078 (HR, 0.86; 95% CI, 0.72-1.02). However, OS was not formally tested in a statistical design in the PD-L1—positive subgroup, but was tested in the overall study population.
To be eligible for enrollment, patients must have had metastatic or inoperably locally advanced TNBC with no prior therapy for their advanced disease with an ECOG performance status of 0 or 1. Prior chemotherapy in the curative setting, including taxanes, were permitted if the treatment-free interval was longer than 12 months.
Regarding safety, most all-grade adverse events (AEs) were similar between arms. The most common grade 3/4 AEs with atezolizumab/nab-paclitaxel and nab-paclitaxel were neutropenia (8% vs 8%), decreased neutrophil count (5% vs 3%), peripheral neuropathy (6% vs 3%), fatigue (4% vs 3%), and anemia (3% vs 3%), respectively.