Lizza E L Hendriks1, Clemence Henon2, Edouard Auclin3, Laura Mezquita2, Roberto Ferrara2, Clarisse Audigier-Valette4, Julien Mazieres5, Corentin Lefebvre5, Audrey Rabeau5, Sylvestre Le Moulec6, Sophie Cousin6, Boris Duchemann7, Cecile le Pechoux8, Angela Botticella8, Samy Ammari9, Anas Gazzah10, Caroline Caramella11, Julien Adam12, Emmanuèle Lechapt13, David Planchard2, Dirk De Ruysscher14, Anne-Marie Dingemans15, Benjamin Besse16. 1. Department of Medical Oncology, Gustave Roussy Cancer Campus, Institut d'Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Department of Pulmonary Diseases, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands. Electronic address: lizza.hendriks@mumc.nl. 2. Department of Medical Oncology, Gustave Roussy Cancer Campus, Institut d'Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 3. Gastrointestinal and Medical Oncology Department, Hôpital Européen Georges Pompidou, Paris, France. 4. Department of Pulmonary Diseases, Centre Hospitalier Toulon Sainte-Musse, Toulon, France. 5. Department of Pulmonary Diseases, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France. 6. Department of Medical Oncology, Institut Bergonie, Bordeaux, France. 7. Department of Pulmonary Diseases, Hopital Avicenne, Paris, France. 8. Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France. 9. Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France; Imagerie par Résonance Magnétique Médicale et Multi-Modalités, IR4M, CNRS, Université Paris-Sud, Université Paris-Saclay, Orsay, France. 10. Department of Medical Oncology, Gustave Roussy Cancer Campus, Institut d'Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Department of Drug Development, Gustave Roussy Cancer Campus, Villejuif, France. 11. Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. 12. Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France. 13. Department of Pathology, Centre Hospitalier Sainte Anne, Paris, France. 14. Department of Radiation Oncology, MAASTRO Clinic, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands. 15. Department of Pulmonary Diseases, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands. 16. Department of Medical Oncology, Gustave Roussy Cancer Campus, Institut d'Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Paris-Sud University, Orsay, France.
Abstract
INTRODUCTION: Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort. METHODS: Data from consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression. RESULTS: A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0-1, 58.5% with a score of 1.5-2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging [n = 73]) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval [CI]: 1.5-2.1) and 2.1 (95% CI: 1.9-2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% [p < 0.001]). The median OS times were 8.6 months (95% CI: 6.8-12.0) with BM and 11.4 months (95% CI: 8.6-13.8) months with no BM (p = 0.035). In the BM subgroup multivariate analysis, corticosteroid use (hazard ratio [HR] = 2.37) was associated with poorer OS, whereas stable BMs (HR = 0.62) and higher ds-GPA classification (HR = 0.48-0.52) were associated with improved OS. CONCLUSION: In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis.
INTRODUCTION: Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort. METHODS: Data from consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression. RESULTS: A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0-1, 58.5% with a score of 1.5-2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging [n = 73]) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval [CI]: 1.5-2.1) and 2.1 (95% CI: 1.9-2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% [p < 0.001]). The median OS times were 8.6 months (95% CI: 6.8-12.0) with BM and 11.4 months (95% CI: 8.6-13.8) months with no BM (p = 0.035). In the BM subgroup multivariate analysis, corticosteroid use (hazard ratio [HR] = 2.37) was associated with poorer OS, whereas stable BMs (HR = 0.62) and higher ds-GPA classification (HR = 0.48-0.52) were associated with improved OS. CONCLUSION: In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis.
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