Shirish M Gadgeel1, Rimas V Lukas2, Jerome Goldschmidt3, Paul Conkling4, Keunchil Park5, Diego Cortinovis6, Filippo de Marinis7, Achim Rittmeyer8, Jyoti D Patel9, Joachim von Pawel10, Carol O'Hear11, Catherine Lai12, Sylvia Hu13, Marcus Ballinger14, Alan Sandler15, Mayank Gandhi16, Lou Fehrenbacher17. 1. University of Michigan, 1500 E. Medical Center Drive, 7217CC, Ann Arbor, MI 48109, USA. Electronic address: sgadgeel@med.umich.edu. 2. Department of Neurology, Northwestern University, 710 N. Lake Shore Drive, Abbott Hall 1114, Chicago, IL 60611, USA. Electronic address: rimas.Lukas@nm.org. 3. Blue Ridge Cancer Care, 2600 Research Center Drive, Suite A, Blacksburg, VA 24060, USA. Electronic address: jerome.goldschmidt@usoncology.com. 4. Virginia Oncology Associates, 5900 Lake Wright Drive, Norfolk, VA 23502, USA. Electronic address: paul.conkling@usoncology.com. 5. Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: kpark@skku.edu. 6. Medical Oncology Unit, AOU San Gerardo, Via Pergolesi 33 Monza, Lombardia 20141, Italy. Electronic address: d.cortinovis@asst-monza.it. 7. European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. Electronic address: filippo.demarinis@ieo.it. 8. Lungenfachklinik Immenhausen, Pneumologische Lehrklinik Universität Göttingen Robert-Koch-Str. 3, 34376 Immenhausen, Germany. Electronic address: a.rittmeyer@lungenfachklinik-immenhausen.de. 9. University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USA. Electronic address: jpatel25@medicine.bsd.uchicago.edu. 10. Asklepios Fachkliniken München-Gauting, Gauting, Germany. Electronic address: j.pawel@asklepios.com. 11. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: ohearc@gene.com. 12. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: lai.catherine@gene.com. 13. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: hu.sylvia@gene.com. 14. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: ballinger.marcus@gene.com. 15. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: sandlera@gene.com. 16. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: gandhi.mayank@gene.com. 17. Kaiser Permanente Medical Center, 975 Sereno Drive, Vallejo, CA 94589, USA. Electronic address: louis.fehrenbacher@gmail.com.
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.
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.
Authors: Sarah B Goldberg; Kurt A Schalper; Scott N Gettinger; Amit Mahajan; Roy S Herbst; Anne C Chiang; Rogerio Lilenbaum; Frederick H Wilson; Sacit Bulent Omay; James B Yu; Lucia Jilaveanu; Thuy Tran; Kira Pavlik; Elin Rowen; Heather Gerrish; Annette Komlo; Richa Gupta; Hailey Wyatt; Matthew Ribeiro; Yuval Kluger; Geyu Zhou; Wei Wei; Veronica L Chiang; Harriet M Kluger Journal: Lancet Oncol Date: 2020-04-03 Impact factor: 41.316
Authors: Stephanie T H Peeters; Evert J Van Limbergen; Lizza E L Hendriks; Dirk De Ruysscher Journal: Cancers (Basel) Date: 2021-04-28 Impact factor: 6.639
Authors: Rimas V Lukas; Jigisha P Thakkar; Massimo Cristofanilli; Sunandana Chandra; Jeffrey A Sosman; Jyoti D Patel; Priya Kumthekar; Roger Stupp; Maciej S Lesniak Journal: J Neurooncol Date: 2022-01-20 Impact factor: 4.130