Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry |
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| Institution: | 1. Thoracic Oncology Department, Toulouse University Hospital, Université Paul Sabatier, Toulouse, France;2. Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA;3. Biostatistics Unit, Institut Claudius Regaud, IUCT-O, Toulouse;4. Thoracic Oncology Department, Lille University Hospital, Lille University, Lille;5. Cancer Medicine Department, Gustave Roussy, Villejuif, Paris Sud University Orsay, Paris France;6. Medical Oncology Department, Peter MacCallum Cancer Institute, Melbourne, Australia;7. Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique Hôpitaux de Marseille, Aix Marseille University, CNRS, INSERM, CRCM, Marseille;8. Respiratory Diseases and Thoracic Oncology Department, Lyon Sud Hospital, Cancer Institute of Hospices Civils de Lyon, Lyon 1 University;9. CHU Bordeaux, Respiratory Diseases Department, Bordeaux, France;10. Faculty of Medical Science, Radboud University Medical Center, Nijmegen, The Netherlands;11. Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, USA;12. Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel;13. Department of Oncology, Haematology, Cantonal Hospital St Gallen, St Gallen, University of Bern, Switzerland;14. Thoracic Oncology Department, University of Colorado Cancer Center, Aurora, USA;15. Department of Thoracic Oncology, CIC1425-CLIP2 Paris-Nord, Bichat-Claude Bernard Hospital, APHP, Paris, France;16. Royal Marsden Hospital, London, UK;17. Cantonal Hospital, Lucerne, Switzerland;18. Department of Medicine, Division of Hematology-Oncology, University of California, Irvine School of Medicine, Orange, USA;19. Department Internal Medicine, University Hospital Basel, Medical Oncology, Basel, Switzerland;20. Department of Oncology, University of Torino, Torino, Italy;21. Medical Oncology Department, Vall d''Hebron Hospital, Vall d''Hebron Institute of Oncology, Barcelona, Spain;22. Center of Hematology and Oncology, University Hospital Zurich, Switzerland;23. Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona;24. Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain;25. Pulmonology Department, Grenoble University Hospital, Grenoble, France;26. Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany;27. University of Bern and Cantonal Hospital, Lucerne, Switzerland |
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| Abstract: | BackgroundAnti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methodsWe conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.ResultsWe studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions: ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent. |
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