The Food and Drug Administration (FDA) granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours express PD-L1 (PD-L1 stained tumour-infiltrating immune cells [IC] of any intensity covering ≥ 1 percent of the tumour area), as determined by an FDA-approved test.
FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic device for selecting TNBC patients for atezolizumab.
Approval was based on IMpassion130 (NCT02425891), a multicenter, international, double-blinded, placebo-controlled, randomized trial that included 902 patients with unresectable locally advanced or metastatic TNBC who had not received prior chemotherapy for metastatic disease.
Patients were randomised (1:1) to receive either atezolizumab (840 mg) or placebo intravenous infusions on days 1 and 15 of every 28-day cycle, plus paclitaxel protein-bound (100 mg/m2) administered via intravenous infusion on days 1, 8, and 15 of every 28-day cycle.
Tumour specimens (archival or fresh) were evaluated prospectively using the VENTANA PD-L1 (SP142) Assay at a central laboratory and the results were used as a stratification factor for randomisation and to define the PD-L1 positive population for pre-specified analyses.
In patients whose tumours express PD-L1, median progression-free survival (PFS) was 7.4 months (6.6, 9.2) for patients receiving atezolizumab with paclitaxel protein-bound and 4.8 months (3.8, 5.5) for those receiving placebo with paclitaxel protein-bound.
The stratified hazard ratio for PFS was 0.60 (95% CI: 0.48, 0.77; p<0.0001) in favour of the atezolizumab plus paclitaxel protein-bound arm.
Objective response rate (ORR) in patients with confirmed responses was 53 percent compared to 33 percent for the atezolizumab and the placebo-containing arms, respectively.
Overall survival data were immature with 43 percent deaths in the intent to treat (ITT) population.
The most common adverse reactions (reported in ≥ 20 percent of patients) with atezolizumab with paclitaxel protein-bound were alopecia, peripheral neuropathies, fatigue, nausea, diarrhoea, anaemia, constipation, cough, headache, neutropenia, vomiting, and decreased appetite.
This indication is approved under accelerated approval based on progression-free survival.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
The recommended atezolizumab dose for patients with TNBC whose tumours express PD-L1 is 840 mg administered as an intravenous infusion over 60 minutes, followed by 100 mg/m2 paclitaxel protein-bound.
For each 28-day cycle, atezolizumab is administered on days 1 and 15, and paclitaxel protein-bound is administered on days 1, 8, and 15 until disease progression or unacceptable toxicity.
Source: U.S. Food & Drug Administration
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