Frost, Nikolaj and Christopoulos, Petros and Kauffmann-Guerrero, Diego and Stratmann, Jan and Riedel, Richard and Schaefer, Monica and Alt, Jurgen and Gutz, Sylvia and Christoph, Daniel C. and Laack, Eckart and Faehling, Martin and Fischer, Richard and Fenchel, Klaus and Haen, Sebastian and Heukamp, Lukas and Schulz, Christian and Griesinger, Frank (2021) Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program. THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 13: 1758835920. ISSN 1758-8340, 1758-8359
Full text not available from this repository. (Request a copy)Abstract
Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib. Patients and Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed. Results: In total, 52 patients were included [median age 57 years (range 32-81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1-4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4 months, 8.0 months, 54% and 13.0 months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6 months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8 month, HR 3.3, p = 0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p = 0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS. Conclusions: Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLINICAL IMPACT; CRIZOTINIB; PROGRESSION; CHEMOTHERAPY; ALECTINIB; SURVIVAL; THERAPY; CNS; ALK; brain metastases; early access program; lorlatinib; NSCLC; ROS1; TP53 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Sep 2022 12:33 |
| Last Modified: | 30 Sep 2022 12:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48122 |
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