FDA Approval Summary: Atezolizumab Plus Paclitaxel Protein-bound for the Treatment of Patients with Advanced or Metastatic TNBC Whose Tumors Express PD-L1

Clin Cancer Res. 2020 May 15;26(10):2284-2289. doi: 10.1158/1078-0432.CCR-19-3545. Epub 2020 Jan 30.

Abstract

On March 8, 2019, the FDA granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 [PD-L1 stained tumor-infiltrating immune cells (IC) of any intensity covering ≥1% of the tumor area], as determined by an FDA-approved test. Approval was based on data from IMpassion130, which randomized patients to receive atezolizumab or placebo in combination with paclitaxel protein-bound. Investigator-assessed progression-free survival (PFS) in the intent-to-treat (ITT) and PD-L1-positive populations were coprimary endpoints. After 13-month median follow-up, the estimated median PFS in the PD-L1-positive population was 7.4 months in the atezolizumab arm and 4.8 months in the placebo arm [HR = 0.60; 95% confidence interval (CI), 0.48-0.77]. Overall survival (OS) results were immature with 43% deaths in the ITT population, representing 59% of the OS events required to perform the final OS analysis. Adverse reactions occurring in ≥20% of patients receiving atezolizumab with paclitaxel protein-bound were alopecia, peripheral neuropathies, fatigue, nausea, diarrhea, anemia, constipation, cough, headache, neutropenia, vomiting, and decreased appetite. Accelerated approval was appropriate taking into account the unmet medical need along with the immaturity of the OS results and potential for PFS in the PD-L1-expressing population to predict clinical benefit.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / immunology
  • Double-Blind Method
  • Drug Approval
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Paclitaxel / administration & dosage
  • Prognosis
  • Survival Rate
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / pathology
  • Vereinigte Staaten
  • United States Food and Drug Administration
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • atezolizumab
  • Paclitaxel