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