The European Commission has approved Tecentriq ( Atezolizumab ) plus chemotherapy ( Abraxane [ Paclitaxel protein-bound particles for injectable suspension ( albumin-bound ); nab-Paclitaxel ] ) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer ( TNBC ) whose tumours have PD-L1 expression ( greater than or equal to 1% ) and who have not received prior chemotherapy for metastatic disease.
VENTANA PD-L1 ( SP142 ) Assay is now CE marked and commercially available in the European Union as an aid for identifying patients with TNBC eligible for treatment with the Tecentriq combination.
This approval is based on the results from the phase III IMpassion130 study. Progression-free survival ( PFS ) results demonstrated a statistically significant benefit for Atezolizumab in combination with nab-Paclitaxel and showed that Atezolizumab plus nab-Paclitaxel significantly reduced the risk of disease worsening or death ( PFS ) by 38% compared with nab-Paclitaxel alone ( median PFS=7.5 vs 5 months; hazard ratio [ HR ]=0.62, 95% CI: 0.49-0.78, p less than 0.0001 ) in people who were tested positive for PD-L1 expression on tumour-infiltrating immune cells.
At the second interim analysis, Atezolizumab and nab-Paclitaxel showed a clinically meaningful overall survival ( OS ) improvement of seven months vs placebo and nab-Paclitaxel in the PD-L1-positive population ( median OS=25.0 vs 18.0 months; HR=0.71, 95% CI: 0.54 –0.93 ).
Overall survival results in the PD-L1-positive population were not formally tested due to the hierarchical design of the study as statistical significance was not met for overall survival in the intention-to-treat ( ITT ) population ( median OS=21.0 vs 18.7 months; HR=0.86, 95% CI: 0.72–1.02, p=0.078 ).
The assessment of PD-L1 on tumour-infiltrating immune cells is essential for identifying the patients with TNBC benefiting from this Atezolizumab combination.
Safety in the Atezolizumab plus nab-Paclitaxel arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.
The nature and incidence of severe adverse events ( SAEs ) and grade 3–4 adverse events were consistent with the known safety profiles of the individual study drugs or the underlying disease.
Severe adverse events were reported in 23% of people receiving Atezolizumab plus nab-Paclitaxel compared to 18% of people receiving chemotherapy alone.
Grade 3–4 adverse events were reported in 49% of people receiving Atezolizumab plus nab-Paclitaxel compared to 42% of people receiving chemotherapy alone.
The IMpassion130 study is a phase III, multicentre, randomised, double-blind study evaluating the efficacy, safety and pharmacokinetics of Atezolizumab plus nab-Paclitaxel compared with placebo plus nab-Paclitaxel in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer.
The study enrolled 902 people who were randomised equally ( 1:1 ).
The co-primary endpoints are progression-free survival per investigator assessment ( RECIST 1.1 ) and overall survival in the ITT population and in the PD-L1-positive population.
Secondary endpoints include objective response rate and duration of response.
Breast cancer is the most common cancer among women with more than 2 million diagnosed worldwide each year.
TNBC represents approximately15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer. It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.
Patients with metastatic TNBC generally experience rapid progression and shorter overall survival compared to other subtypes of breast cancer. ( Xagena )
Source: Roche, 2019