Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study

Lung Cancer. 2019 Feb;128:105-112. doi: 10.1016/j.lungcan.2018.12.017. Epub 2018 Dec 19.

Abstract

Objectives: To assess the safety and efficacy of atezolizumab and docetaxel in patients with and without a history of asymptomatic, treated brain metastases in the phase III OAK trial.

Materials and methods: Patients received 1200 mg atezolizumab or 75 mg/m2 docetaxel every 3 weeks until unacceptable toxicity, disease progression, or loss of clinical atezolizumab benefit. Patients with asymptomatic, treated supratentorial metastases were eligible. Patients had brain scans before enrollment; follow-up brain scans and treatment were required when clinically indicated.

Results: Approximately 14% of patients in each arm had a history of asymptomatic, treated brain metastases (61/425 in the atezolizumab arm and 62/425 in the docetaxel arm). Fewer treatment-related adverse events (AEs), serious AEs, and treatment-related neurologic AEs were reported with atezolizumab than with docetaxel, regardless of history of asymptomatic, treated brain metastases. In patients with a history of asymptomatic, treated brain metastases, median overall survival (OS) was longer with atezolizumab than with docetaxel (16.0 vs 11.9 months; hazard ratio = 0.74; 95% CI: 0.49-1.13). Median OS was also longer with atezolizumab in patients without a history of asymptomatic, treated brain metastases (13.2 vs 9.3 months; hazard ratio = 0.74; 95% CI: 0.63-0.88). Landmark analyses showed that patients with a history of asymptomatic, treated brain metastases had a lower probability of developing new symptomatic brain lesions with atezolizumab vs docetaxel at 6-24 months. Patients without a history had a lower probability with atezolizumab at 18-24+ months.

Conclusion: Atezolizumab had an acceptable neurologic safety profile, showed a trend toward an OS benefit, and led to a prolonged time to radiographic identification of new symptomatic brain lesions compared with docetaxel in patients who had a history of asymptomatic, treated brain metastases. Clinicaltrials.gov registration number: NCT02008227.

Keywords: Atezolizumab; Brain; Central nervous system; Metastasis; Non-small cell lung cancer (5/6).

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asymptomatic Diseases
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Neoplasm Staging
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • atezolizumab

Associated data

  • ClinicalTrials.gov/NCT02008227