Science and Research

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

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.

  • Peled, N.
  • Gillis, R.
  • Kilickap, S.
  • Froesch, P.
  • Orlov, S.
  • Filippova, E.
  • Demirci, U.
  • Christopoulos, P.
  • Cicin, I.
  • Basal, F. B.
  • Yilmaz, C.
  • Fedor, M.
  • Korkmaz, T.
  • Paydas, S.
  • Gautschi, O.
  • Zirtiloglu, A.
  • Eralp, Y.
  • Cinkir, H. Y.
  • Sezer, A.
  • Erman, M.
  • Tural, D.
  • Turna, H.
  • Mazieres, J.
  • Dudnik, E.
  • Reguart, N.
  • Camidge, D. R.
  • Ng, T. L.
  • Senler, F. C.
  • Beypinar, I.
  • Yazilitas, D.
  • Demirkazik, A.
  • Karaoglu, A.
  • Okutur, K.
  • Coskun, H. S.
  • Sendur, M. A. N.
  • Isikdogan, A.
  • Cabuk, D.
  • Yumuk, P. F.
  • Yildiz, I.
  • Kaplan, M. A.
  • Ozyilkan, O.
  • Oztop, I.
  • Olmez, O. F.
  • Aydin, K.
  • Aydiner, A.
  • Meydan, N.
  • Grinberg, R. D.
  • Roisman, L. C.

Keywords

  • Alk
  • Lorlatinib
  • Ros1
  • Real-world data
Publication details
DOI: 10.1016/j.lungcan.2020.07.022
Journal: Lung Cancer
Pages: 48-54 
Work Type: Original
Location: TLRC
Disease Area: LC
Partner / Member: Thorax
Access-Number: 32799090
See publication on PubMed

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