Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study

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N. Girard¹  S. Galland-Girodet³  V. Avrillon⁴  B. Besse⁵  M. Duruisseaux⁷  J. Cadranel^1,11  J. Otto^1,12  A. Prevost^1,13  B. Roch^1,14  J. Bennouna^1,17  K. Bouledrak^1,18  M. Coudurier^1,19  T. Egenod^2,20  R. Lamy^2,21  C. Ricordel^2,22  D. Moro-Sibilot^2,23  L. Odier^2,24  J. Tillon-Strozyk^2,25  G. Zalcman^2,26  P. Missy^2,27  V. Westeel^2,28  S. Baldacci^2,29 

[1] Institut Curie, Institut du Thorax Curie-Montsouris;Université Versailles Saint Quentin, Paris Saclay Campus;Service d’Oncologie – Radiothérapie, Polyclinique Bordeaux Nord Aquitaine;Service d’Oncologie Médicale, Centre Léon Bérard;Department of Cancer Medicine, Institut Gustave Roussy;Paris-Saclay University;Unité de Recherche Commune en Oncologie Thoracique ,(URCOT), Institut de Cancérologie des Hospices Civils de Lyon;Service de Pneumologie, Hôpital Louis Pradel;Oncopharmacology Laboratory, Cancer Research Center of Lyon;Université Claude Bernard Lyon 1, Université de Lyon;Chest Department, AP-HP Hôpital Tenon and GRC#4 Theranoscan Sorbonne Université Paris;Oncologie, Centre Anticancer Antoine Lacassagne;Institut Godinot;Unité d’Oncologie Thoracique, Département de Pneumologie;Institut de Recherche en Cancérologie de Montpellier, U1194, Campus Val d’Aurelle;Université de Montpellier;Thoracic Oncology Unit, University Hospital of Nantes;Oncologie Médicale et Pneumologie, Hôpital Privé Jean Mermoz;Pneumologie, Centre hospitalier Métropole Savoie;Thoracic Oncology Department, CHU Limoges – Hôpital Dupuytren;Oncologie;Department of Pulmonary Medicine;Thoracic Oncology, CHU de Grenoble, Hôpital Michallon;Pneumology, L’Hôpital Nord Ouest Villefranche-Sur-Saône;Clinique Pneumologique, Hôpital Charles Nicolle;Department of Thoracic Oncology and CIC1425, Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université Paris-Diderot;French Cooperative Thoracic Intergroup;Oncologie Thoracique et Allergologie Respiratoire, CHRU Besancon – Hôpital Jean Minjoz;Lille University, CHU Lille, Thoracic Oncology Department, CNRS, Inserm, Institut Pasteur de Lille

关键词: NSCLC;    ROS1;    chemotherapy;    brain metastases;   

DOI  :  10.1016/j.esmoop.2022.100418

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Introduction ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program.Methods Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival.Results Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data.Conclusions Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.

【 授权许可】

CC BY|CC BY-NC-ND