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. (February 2019)

• Record Type: Journal Article
• Authors: Gadgeel, Shirish M.; Lukas, Rimas V.; Goldschmidt, Jerome; Conkling, Paul; Park, Keunchil; Cortinovis, Diego; de Marinis, Filippo; Rittmeyer, Achim; Patel, Jyoti D.; von Pawel, Joachim; O'Hear, Carol; Lai, Catherine; Hu, Sylvia; Ballinger, Marcus; Sandler, Alan; Gandhi, Mayank; Fehrenbacher, Lou
• Is Part Of: Lung cancer. Volume 128(2019)
• Page Start: 105
• Page End: 112
• Publication Date: 2019-02
• Subjects: AE adverse event -- CNS central nervous system -- CRF case report form -- ECOG Eastern Cooperative Oncology Group -- HR hazard ratio -- IC tumor-infiltrating immune cells -- ITT intention-to-treat -- NE not evaluable -- NSCLC non-small cell lung cancer -- OS overall survival -- PD-1 programmed death-1 -- PD-L1 programmed death-ligand 1 -- RECIST Response Evaluation Criteria in Solid Tumors -- SAE serious adverse event -- TC tumor cells; Atezolizumab -- Brain -- Central nervous system -- Metastasis -- Non-small cell lung cancer (5/6); Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.12.017
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Compared with docetaxel in patients who had a history of treated brain metastases. Atezolizumab had an acceptable neurologic safety profile. Atezolizumab showed a trend toward overall survival benefit. Atezolizumab prolonged time to identification of new symptomatic brain lesions. 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/m 2 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.