학술논문
Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05).
Document Type
Academic Journal
Author
Nadal E; Department of Medical Oncology, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.; Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Rodríguez-Abreu D; Department of Medical Oncology, Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.; Simó M; Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO, IDIBELL, L'Hospitalet, Barcelona, Spain.; Massutí B; Department of Medical Oncology, Hospital General de Alicante, Alicante, Spain.; Juan O; Department of Medical Oncology, Hospital Universitari La Fe, Valencia, Spain.; Huidobro G; Department of Medical Oncology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain.; López R; Department of Medical Oncology, Hospital Clínico de Valladolid, Valladolid, Spain.; De Castro J; Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain.; Estival A; Department of Medical Oncology, Institut Català d'Oncologia (ICO), Badalona, Spain.; Mosquera J; Department of Medical Oncology, Hospital Universitario A Coruña, A Coruña, Spain.; Sullivan I; Department of Medical Oncology, Hospital Sant Pau, Barcelona, Spain.; Felip E; Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.; Blasco A; Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain.; Guirado M; Department of Medical Oncology, Hospital Universitario de Elche, Elche, Spain.; Pereira E; Spanish Lung Cancer Group, Barcelona, Spain.; Vilariño N; Department of Medical Oncology, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.; Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO, IDIBELL, L'Hospitalet, Barcelona, Spain.; Navarro V; Department of Medical Oncology, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.; Bruna J; Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO, IDIBELL, L'Hospitalet, Barcelona, Spain.
Source
Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: The Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials.
Methods: This single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade ≥3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria.
Results: Forty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5).
Conclusion: Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.
Methods: This single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade ≥3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria.
Results: Forty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5).
Conclusion: Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.