INTRODUCTION: In the phase 3 study involving the use of durvalumab with or without tremelimumab in combination with platinum-based chemotherapy in untreated extensive-stage SCLC (CASPIAN study), first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone (p = 0.0047). We report exploratory subgroup analyses of treatment patterns and outcomes according to the presence of baseline brain or central nervous system metastases. METHODS: Patients (WHO performance status 0 or 1), including those with asymptomatic or treated-and-stable brain metastases, were randomized to four cycles of durvalumab plus EP followed by maintenance durvalumab until progression or up to six cycles of EP and optional prophylactic cranial irradiation. Prespecified analyses of OS and progression-free survival (PFS) in subgroups with or without brain metastases used unstratified-Cox proportional hazards models. The data cutoff was on January 27, 2020. RESULTS: At baseline, 28 out of 268 patients (10.4%) in the durvalumab plus EP arm and 27 out of 269 patients (10.0%) in the EP arm had known brain metastases, of whom 3 of 28 (10.7%) and 4 of 27 (14.8%) had previous brain radiotherapy, respectively. Durvalumab plus EP (versus EP alone) prolonged OS (hazard ratio, 95% confidence interval) in patients with (0.79, 0.44-1.41) or without (0.76, 0.62-0.92) brain metastases, with similar PFS results (0.73, 0.42-1.29 and 0.80, 0.66-0.97, respectively). Among patients without brain metastases, similar proportions in each arm developed new brain lesions as part of their first progression (8.8% and 9.5%), although 8.3% in the EP arm received prophylactic cranial irradiation. Similar proportions in each arm received subsequent brain radiotherapy (20.5% and 21.2%), although more common in patients with than without baseline brain metastases (45.5% and 18.0%). CONCLUSIONS: The OS and PFS benefit with first-line durvalumab plus EP were maintained irrespective of the presence of brain metastases, further supporting its standard-of-care use.

AstraZeneca Cambridge United Kingdom

AstraZeneca Gaithersburg Maryland

Azienda Ospedaliera Vincenzo Cervello Palermo Italy

Cancer and Hematology Centers of Western Michigan Grand Rapids Michigan

Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan

David Geffen School of Medicine at University of California Los Angeles Los Angeles California

Department of Internal Medicine Samsung Changwon Hospital Sungkyunkwan University School of Medicine Changwon South Korea

Department of Medical Oncology Hospital Universitario 12 de Octubre Madrid Spain

Department of Pneumology 1st Faculty of Medicine Thomayer Hospital Charles University Prague Czechia

Department of Pulmonology Semmelweis University Budapest Hungary

Department of Respiratory and Critical Care Medicine Karl Landsteiner Institute of Lung Research and Pulmonary Oncology Krankenhaus Nord Vienna Austria

Department of Thoracic Oncology Asklepios Lung Clinic Munich Gauting Germany

Division of Medical Oncology Department of Internal Medicine Cerrahpaşa School of Medicine Istanbul University Cerrahpaşa Istanbul Turkey

Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

Medical Oncology UMHAT St Marina Varna Bulgaria

Omsk Regional Cancer Center Omsk Russia

Section of Hematology Oncology The University of Chicago Chicago Illinois

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