GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients. (October 2020)

• Record Type: Journal Article
• Authors: Peled, Nir; Gillis, Roni; Kilickap, Saadettin; Froesch, Patrizia; Orlov, Sergei; Filippova, Elena; Demirci, Umut; Christopoulos, Petros; Cicin, Irfan; Basal, Fatma Bugdayci; Yilmaz, Cengiz; Fedor, Moiseenko; Korkmaz, Taner; Paydas, Semra; Gautschi, Oliver; Zirtiloglu, Alisan; Eralp, Yesim; Cinkir, Havva Yesil; Sezer, Ahmet; Erman, Mustafa; Tural, Deniz; Turna, Hande; Mazieres, Julien; Dudnik, Elizabeth; Reguart, Noemi; Camidge, David Ross; Ng, Terry L.; Şenler, Filiz Çay; Beypınar, İsmail; Yazılıtaş, Doğan; Demirkazık, Ahmet; Karaoğlu, Aziz; Okutur, Kerem; Coşkun, Hasan Şenol; Şendur, Mehmet Ali Nahit; Isikdogan, Abdurrahman; Cabuk, Devrim; Yumuk, Perran Fulden; Yıldız, Ibrahim; Kaplan, M. Ali; Özyılkan, Özgür; Öztop, İlhan; Olmez, Omer Fatih; Aydin, Kübra; Aydıner, Adnan; Meydan, Nezih; Grinberg, Roxana Denisa; Roisman, Laila C.;
• Is Part Of: Lung cancer. Volume 148(2020)
• Page Start: 48
• Page End: 54
• Publication Date: 2020-10
• Subjects: Lorlatinib -- Real-world data -- ALK -- ROS1; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.07.022
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Lorlatinib is highly extracranial (EC) and intracranial (IC) effective for ALK+ or ROS1+ in advanced NSCLC. Response rates (RR) of EC 60% and IC 62% for ALK + and EC and IC RR of 62% and 67% for ROS1+, respectively. Mean duration of therapy (DoT) for ALK + was 23.9 ± 1.6 months and median overall survival (mOS) 89.1 ± 19.6 months. ROS1 + cohort had a median DoT of 18.1 ± 2.5 months and mOS of 90.3 ± 24.4 months. Abstract: Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK / ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK (+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. Results: 106 ALK (+) and 17 ROS1 (+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ± 1.6 months and median overall survival (mOS) was 89.1 ± 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ± 2.5 months and mOS of 90.3 ± 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1–2 were reported in 18 % of patients. Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK / ROS1(+) NSCLC. The observed mOS of 89 ± 19 months in ALK (+) NSCLC supports previous reports, while mOS from of 90 ± 24 months is unprecedented for ROS1(+) NSCLC.