WCLC 2018 — ES-SCLC: 1L atezolizumab hits the mark in IMpower133


  • Brian Hoyle
  • Univadis
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Takeaway

  • IMpower133 is the first study in decades to demonstrate a clinically meaningful improvement in OS in extensive stage (ES)-SCLC compared with the standard of care.

Why this matters

  • Little progress in the treatment of ES-SCLC for 2 decades.
  • Current standard of care is typically platinum (carboplatin or cisplatin) plus etoposide.
  • Outcomes are poor, with a median OS of approximately 10 months.
  • Immunotherapy has potential in the treatment of refractory or metastatic SCLC.
  • There may be synergy between immunotherapy targeting programmed death ligand 1 (PD-L1) and chemotherapy.
  • Atezolizumab is a humanized monoclonal anti-PD-L1 antibody.

Study design

  • IMpower133 (NCT02763579) evaluated the efficacy and safety of first-line atezolizumab, or placebo, plus carboplatin and etoposide, in ES-SCLC.
  • 403 patients with ES-SCLC, ECOG PS 0 or 1, no prior systemic treatment for ES-SCLC.
  • Patients with treated asymptomatic brain metastases were eligible.
  • Patients stratified by sex (male vs female), Eastern Cooperative Oncology Group Performance Status (0 vs 1), and brain metastases (yes or no).
  • Patients randomly assigned 1:1 to atezolizumab (1200 mg intravenous on day 1)+carboplatin and etoposide (n=201) or placebo+carboplatin and etoposide (n=202).
  • Maintenance with atezolizumab or placebo.
  • Treat until disease progression or loss of clinical effect.
  • Co-primary endpoints: OS and investigator-assessed PFS.
  • Key secondary endpoints: objective response rate, duration of response, safety.

Key results

  • Two groups balanced at baseline.
  • 12-month OS: 51.7% in the atezolizumab group, 38.2% in the placebo group.
  • Median OS: 12.3 months (95% CI, 10.8-15.9 months) in the atezolizumab group, 10.3 months (95% CI, 9.3-11.3 months) in the placebo group (HR, 0.70; 95% CI, 0.54-0.91; P=.0069).
  • 12-month PFS: 12.6% in the atezolizumab group, 5.4% in the placebo group.
  • Median PFS: 5.2 months (95% CI, 4.4-5.6 months) in the atezolizumab group, 4.3 months (95% CI, 4.2-4.5 months) in the placebo group (HR, 0.77; 95% CI, 0.62-0.96; P=.017).
  • Median duration of response: 4.2 months (95% CI, 1.4-19.5 months) in the atezolizumab group, 3.9 months (95% CI, 2.0-16.1 months) in the placebo group (HR, 0.70; 95% CI, 0.53-092).
  • Rates of hematologic adverse effects were similar between the study groups.
  • More adverse event-related withdrawals were seen in the atezolizumab group (10.6% vs 2.6%), mainly because of rash.

Expert comment

  • "IMpower133 is the first study in >20 years to show a clinically meaningful improvement in OS over the current standard of care in first-line ES-SCLC. The data suggest that atezolizumab plus carboplatin and etoposide is a new standard of care for the first-line treatment of ES-SCLC," said presenter Steven V. Liu, MD, Georgetown University, Washington, DC.