Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program
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...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 9, 2021
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| In: |
Therapeutic advances in medical oncology
Year: 2021, Volume: 13, Pages: 1-15 |
| ISSN: | 1758-8359 |
| DOI: | 10.1177/1758835920980558 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1177/1758835920980558
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| Author Notes: | Nikolaj Frost, Petros Christopoulos, Diego Kauffmann-Guerrero, Jan Stratmann, Richard Riedel, Monica Schaefer, Jürgen Alt, Sylvia Gütz, Daniel C. Christoph, Eckart Laack, Martin Faehling, Richard Fischer, Klaus Fenchel, Sebastian Haen, Lukas Heukamp, Christian Schulz and Frank Griesinger |
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| 245 | 1 | 0 | |a Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations |b results from the German early access program |c Nikolaj Frost, Petros Christopoulos, Diego Kauffmann-Guerrero, Jan Stratmann, Richard Riedel, Monica Schaefer, Jürgen Alt, Sylvia Gütz, Daniel C. Christoph, Eckart Laack, Martin Faehling, Richard Fischer, Klaus Fenchel, Sebastian Haen, Lukas Heukamp, Christian Schulz and Frank Griesinger |
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| 520 | |a 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. | ||
| 650 | 4 | |a ALK | |
| 650 | 4 | |a brain metastases | |
| 650 | 4 | |a early access program | |
| 650 | 4 | |a lorlatinib | |
| 650 | 4 | |a NSCLC | |
| 650 | 4 | |a ROS1 | |
| 650 | 4 | |a TP53 | |
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