A supplemental biologics license application for the frontline combination of atezolizumab plus nab-paclitaxel has been granted a priority review by the FDA for the treatment of patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer, based on data from the phase III IMpassion130 trial.
Sandra Horning, MD
A supplemental biologics license application (sBLA) for the frontline combination of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) has been granted a priority review by the FDA for the treatment of patients with unresectable locally advanced or metastatic PD-L1positive triple-negative breast cancer (TNBC), based on data from the phase III IMpassion130 trial.
Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision on the sBLA by March 12, 2019.
Findings of the double-blind phase III trial showed 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.
“Tecentriq in combination with nab-paclitaxel has the potential to meaningfully advance treatment for people with PD-L1-positive, metastatic triple-negative breast cancer. People need more options for this type of breast cancer, which is particularly difficult to treat,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech (Roche), the manufacturer of atezolizumab, said in a statement. “We are working closely with the FDA to bring this Tecentriq combination to people with PD-L1-positive, metastatic triple-negative breast cancer as soon as possible,” added Horning.
The study evaluated the efficacy and safety of atezolizumab 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/m2intravenously 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-L1positive 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-L1positive population demonstrated a clinically meaningful median PFS of 7.5 months (95% CI, 6.7-9.2) with atezolizumab/nab-paclitaxel and 5.0 months (95% CI, 3.8-5.6) with chemotherapy (HR, 0.62; 95% CI, 0.49-0.78;P<.0001). 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.
At a 12.9-month follow-up, an interim OS analysis of the PD-L1positive population showed a clinically meaningful improvement with added atezolizumab at 25.0 months versus nab-paclitaxel alone at 15.5 months (HR, 0.62; 95% CI, 0.45-0.86). 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 .0840 (HR, 0.84; 95% CI, 0.69-1.02). However, OS was not formally tested in a statistical design.
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.
Schmid P. IMpassion130: Results from a global, randomised, double-blind, phase 3 study of atezolizumab (atezo) + nab-paclitaxel (nab-P) vs placebo + nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC). In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA1_PR.