The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted an Early Access to Medicines Scheme (EAMS) positive scientific opinion to atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) for patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer (TNBC).
The EAMS is designed to give patients with life-threatening or seriously debilitating conditions access to therapies that do not yet have a marketing authorization when there is a clear unmet medical need. Under the EAMS, the MHRA provides a scientific opinion on the benefit/risk balance of the treatment, based on the available data when the submission was made.
The MHRA’s opinion is based on findings from the phase III IMpassion130 trial, in which the addition of the PD-L1 inhibitor atezolizumab to nab-paclitaxel was found to reduce the risk of progression or death by 40% compared with nab-paclitaxel alone in patients with unresectable locally advanced or metastatic PD-L1–positive TNBC.
In the IMpassion130 trial, investigators evaluated the efficacy and safety of the PD-L1 inhibitor plus chemotherapy versus nab-paclitaxel alone in treatment-naïve patients with metastatic TNBC. In the study, patients were randomized 1:1 to receive nab-paclitaxel at 100 mg/m2
intravenously (IV) on days 1, 8, and 15 of the 28-day cycle with atezolizumab at 840 mg IV (n = 451) on days 1 and 15 of a 28-day cycle or with placebo (n = 451). The therapy 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.
Findings of the primary PFS analysis in the PD-L1–positive population demonstrated a clinically meaningful median PFS of 7.4 months with atezolizumab/nab-paclitaxel and 4.8 months with chemotherapy (HR, 0.60; 95% CI, 0.48-0.77; P
<.0001). Additionally, the 1-year PFS rates were 29% (95% CI, 22%-36%) with atezolizumab/nab-paclitaxel and 16% (95% CI, 11%-22%) with nab-paclitaxel.
Moreover, 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). The 1-year PFS rates were 24% (95% CI, 20%-28%) with atezolizumab and 18% (95% CI, 14%-21%) with nab-paclitaxel.
At a 12.9-month follow-up, an interim OS analysis of the PD-L1–positive population showed a clinically meaningful improvement with the addition of atezolizumab at 25.0 months versus nab-paclitaxel alone at 15.5 months (HR, 0.62; 95% CI, 0.45-0.86). The 2-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 in the PD-L1–positive subgroup, although it was evaluated in the overall study population.
To be eligible for enrollment on IMpassion130, 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 >12 months.
Regarding safety, the majority of all-grade adverse events (AEs) were similar between the 2 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.
The EAMS opinion follows the March 2019 FDA approval for the frontline regimen for patients with unresectable locally advanced or metastatic PD-L1–positive TNBC, also based on the double-blind phase III IMpassion130 trial. The FDA approval of the atezolizumab combination in this setting is contingent on the results of a confirmatory trial.
- Early Access to Medicines Scheme (EAMS) Scientific Opinion: Atezolizumab as 1st Line Treatment of Adults With Unresectable Locally Advanced Or Metastatic Triple-Negative Breast Cancer (TNBC) Whose Tumours Have PD-L1 Expression ≥ 1%. Gov.UK. Published March 13, 2019. https://bit.ly/2F68G2v. Accessed March 14, 2019.
- 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.