Author(s): Ernest Nadal, MD, PhD1,2; Delvys Rodríguez-Abreu, MD3; Marta Simó, MD, PhD4; Bartomeu Massutí, MD, PhD5; Oscar Juan, MD, PhD6; Gerardo Huidobro, MD7; Rafael López, MD8; Javier De Castro, MD, PhD9; Anna Estival, MD, PhD10; Joaquín Mosquera, MD11; Ivana Sullivan, MD, PhD12; Enriqueta Felip, MD, PhD13; Ana Blasco, MD14; Maria Guirado, MD15; Eva Pereira, BoS16; Noelia Vilariño, MD1,2,4; Valentín Navarro, PhD1; and Jordi Bruna, MD, PhD4
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.
Author Affiliations
1Department of Medical Oncology, Institut Català d’Oncologia (ICO), L’Hospitalet de Llobregat, Barcelona, Spain; 2Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; 3Department 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; 4Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO, IDIBELL, L’Hospitalet, Barcelona, Spain; 5Department of Medical Oncology, Hospital General de Alicante, Alicante, Spain; 6Department of Medical Oncology, Hospital Universitari La Fe, Valencia, Spain; 7Department of Medical Oncology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; 8Department of Medical Oncology, Hospital Clínico de Valladolid, Valladolid, Spain; 9Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain; 10Department of Medical Oncology, Institut Català d’Oncologia (ICO), Badalona, Spain; 11Department of Medical Oncology, Hospital Universitario A Coruña, A Coruña, Spain; 12Department of Medical Oncology, Hospital Sant Pau, Barcelona, Spain; 13Department of Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain; 14Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain; 15Department of Medical Oncology, Hospital Universitario de Elche, Elche, Spain; 16Spanish Lung Cancer Group, Barcelona, Spain
