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

Shirish M. Gadgeel*, Rimas V. Lukas, Jerome Goldschmidt, Paul Conkling, Keunchil Park, Diego Cortinovis, Filippo de Marinis, Achim Rittmeyer, Jyoti D. Patel, Joachim von Pawel, Carol O'Hear, Catherine Lai, Sylvia Hu, Marcus Ballinger, Alan Sandler, Mayank Gandhi, Lou Fehrenbacher

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalLung Cancer
Volume128
DOIs
StatePublished - Feb 2019

Keywords

  • Atezolizumab
  • Brain
  • Central nervous system
  • Metastasis
  • Non-small cell lung cancer (5/6)

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Gadgeel, S. M., Lukas, R. V., Goldschmidt, J., Conkling, P., Park, K., Cortinovis, D., de Marinis, F., Rittmeyer, A., Patel, J. D., von Pawel, J., O'Hear, C., Lai, C., Hu, S., Ballinger, M., Sandler, A., Gandhi, M., & Fehrenbacher, L. (2019). 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, 128, 105-112. https://doi.org/10.1016/j.lungcan.2018.12.017