EU Panel Endorses Atezolizumab in PD-L1+, Metastatic TNBC

Nick Mulcahy

Disclosures

June 28, 2019

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of atezolizumab (Tecentriq, Roche) plus nab-paclitaxel (Abraxane, Celgene) for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer with PD-L1 expression (≥1%) for patients who have not yet received chemotherapy for metastatic disease.

The CHMP recommendation is based on the latest safety and efficacy data from the IMpassion130 study, a phase 3 trial that compared the combination therapy (n = 451) with nab-paclitaxel alone (n = 451).

The investigators indicated that atezolizumab plus nab-paclitaxel significantly reduced the risk for disease worsening or death (progression-free survival [PFS]) by 38% compared with nab-paclitaxel alone (median PFS = 7.5, vs 5 months; hazard ratio [HR] = 0.62; P < .0001) in participants with PD-L1 expression on tumor-infiltrating immune cells.

PD-L1 expression status was assessed with the Ventana PD-L1 (SP142) assay.

In the study's intention-to-treat (ITT) population, which included patients without PD-L1 expression, the overall survival (OS) benefit in the combination-therapy group was not statistically significant in comparison with the patients who received nab-paclitaxel alone (median OS = 21.0 vs 18.7 months; HR = 0.86; P = .078).

The trial design requires that testing for statistical significance for OS in the PD-L1-positive population be dependent upon OS results from all randomized patients.

The study will continue until the next planned analysis.

Safety in the atezolizumab plus nab-paclitaxel arm appeared consistent with the known safety profiles of the individual study medicines or underlying disease. No new safety signals were identified with the combination, according to a company statement.

Serious adverse events were reported in 23% of the combination therapy group, compared with 18% of the patients who received nab-paclitaxel. Grade 3–4 AEs were reported in 49% of the combination-therapy group, vs 42% of the nab-paclitaxel group.

In March, the US Food and Drug Administration granted accelerated approval of atezolizumab plus nab-paclitaxel in this setting.

The approval was based on earlier PFS results from the study's first interim analysis, which were presented at the European Society for Medical Oncology 2018 Congress and were simultaneously published in the New England Journal of Medicine.

At that time, the study was controversially championed by some experts as improving overall survival in the trial's PD-L1+ subgroup.

However, earlier this month, the investigators reported their second interim analysis at the American Society of Clinical Oncology annual meeting. They said that there was no significant overall survival benefit with atezolizumab vs placebo, either in the intention-to-treat population or in the PD-L1-positive subgroup.

The IMpassion130 trial is sponsored by Roche.

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