Atezolizumab Plus Nab-Paclitaxel Approved in Europe for Frontline TNBC

Sandra Horning, MD, chief medical officer and head of Global Product Development, Roche

Sandra Horning, MD

The European Commission (EC) has approved 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), according to Roche (Genentech), the manufacturer of the PD-L1 inhibitor.

The approval, 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 EC simultaneously granted marketing authorization to Roche’s VENTANA PD-L1 (SP142) Assay to identify patients with TNBC whose PD-L1 levels make them eligible for treatment with the atezolizumab/nab-paclitaxel regimen.

“For the past 30 years, we have been dedicated to transforming the lives of people with breast cancer. Now, we are pleased to build on this foundation with the news that the first immunotherapy treatment for triple-negative breast cancer is available to people in Europe with PD-L1—positive, metastatic triple-negative breast cancer,” Sandra Horning, MD, Roche’s chief medical officer and head of global product development, said in a statement.

“The European approval of this Tecentriq combination represents a significant step forward in the treatment of this aggressive breast cancer, where the unmet medical need is great,” added Horning.

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.

References

1. CHMP recommends EU approval of Roche’s Tecentriq in combination with Abraxane as an initial treatment for people with PD-L1-positive, metastatic triple-negative breast cancer [news release]. Roche. Published on June 28, 2019. https://bit.ly/2RItKSl. Accessed June 28, 2019.
2. 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.