PMID- 30642441 OWN - NLM STAT- MEDLINE DCOM- 20191220 LR - 20191220 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 128 DP - 2019 Feb TI - 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. PG - 105-112 LID - S0169-5002(18)30714-1 [pii] LID - 10.1016/j.lungcan.2018.12.017 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Gadgeel, Shirish M AU - Gadgeel SM AD - University of Michigan, 1500 E. Medical Center Drive, 7217CC, Ann Arbor, MI 48109, USA. Electronic address: sgadgeel@med.umich.edu. FAU - Lukas, Rimas V AU - Lukas RV AD - Department of Neurology, Northwestern University, 710 N. Lake Shore Drive, Abbott Hall 1114, Chicago, IL 60611, USA. Electronic address: rimas.Lukas@nm.org. FAU - Goldschmidt, Jerome AU - Goldschmidt J AD - Blue Ridge Cancer Care, 2600 Research Center Drive, Suite A, Blacksburg, VA 24060, USA. Electronic address: jerome.goldschmidt@usoncology.com. FAU - Conkling, Paul AU - Conkling P AD - Virginia Oncology Associates, 5900 Lake Wright Drive, Norfolk, VA 23502, USA. Electronic address: paul.conkling@usoncology.com. FAU - Park, Keunchil AU - Park K AD - Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: kpark@skku.edu. FAU - Cortinovis, Diego AU - Cortinovis D AD - Medical Oncology Unit, AOU San Gerardo, Via Pergolesi 33 Monza, Lombardia 20141, Italy. Electronic address: d.cortinovis@asst-monza.it. FAU - de Marinis, Filippo AU - de Marinis F AD - European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. Electronic address: filippo.demarinis@ieo.it. FAU - Rittmeyer, Achim AU - Rittmeyer A AD - Lungenfachklinik Immenhausen, Pneumologische Lehrklinik Universitat Gottingen Robert-Koch-Str. 3, 34376 Immenhausen, Germany. Electronic address: a.rittmeyer@lungenfachklinik-immenhausen.de. FAU - Patel, Jyoti D AU - Patel JD AD - University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USA. Electronic address: jpatel25@medicine.bsd.uchicago.edu. FAU - von Pawel, Joachim AU - von Pawel J AD - Asklepios Fachkliniken Munchen-Gauting, Gauting, Germany. Electronic address: j.pawel@asklepios.com. FAU - O'Hear, Carol AU - O'Hear C AD - Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: ohearc@gene.com. FAU - Lai, Catherine AU - Lai C AD - Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: lai.catherine@gene.com. FAU - Hu, Sylvia AU - Hu S AD - Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: hu.sylvia@gene.com. FAU - Ballinger, Marcus AU - Ballinger M AD - Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: ballinger.marcus@gene.com. FAU - Sandler, Alan AU - Sandler A AD - Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: sandlera@gene.com. FAU - Gandhi, Mayank AU - Gandhi M AD - Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: gandhi.mayank@gene.com. FAU - Fehrenbacher, Lou AU - Fehrenbacher L AD - Kaiser Permanente Medical Center, 975 Sereno Drive, Vallejo, CA 94589, USA. Electronic address: louis.fehrenbacher@gmail.com. LA - eng SI - ClinicalTrials.gov/NCT02008227 PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181219 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 52CMI0WC3Y (atezolizumab) SB - IM MH - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Agents, Immunological/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Asymptomatic Diseases MH - Brain Neoplasms/secondary/therapy MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/*pathology MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/*pathology MH - Male MH - Neoplasm Staging MH - Proportional Hazards Models MH - Treatment Outcome OTO - NOTNLM OT - Atezolizumab OT - Brain OT - Central nervous system OT - Metastasis OT - Non-small cell lung cancer (5/6) EDAT- 2019/01/16 06:00 MHDA- 2019/12/21 06:00 CRDT- 2019/01/16 06:00 PHST- 2018/05/29 00:00 [received] PHST- 2018/12/11 00:00 [revised] PHST- 2018/12/17 00:00 [accepted] PHST- 2019/01/16 06:00 [entrez] PHST- 2019/01/16 06:00 [pubmed] PHST- 2019/12/21 06:00 [medline] AID - S0169-5002(18)30714-1 [pii] AID - 10.1016/j.lungcan.2018.12.017 [doi] PST - ppublish SO - Lung Cancer. 2019 Feb;128:105-112. doi: 10.1016/j.lungcan.2018.12.017. Epub 2018 Dec 19.