dc.contributor.author
Frost, Nikolaj
dc.contributor.author
Christopoulos, Petros
dc.contributor.author
Kauffmann-Guerrero, Diego
dc.contributor.author
Stratmann, Jan
dc.contributor.author
Riedel, Richard
dc.contributor.author
Schaefer, Monica
dc.contributor.author
Alt, Jürgen
dc.contributor.author
Gütz, Sylvia
dc.contributor.author
Christoph, Daniel C.
dc.contributor.author
Laack, Eckart
dc.contributor.author
Faehling, Martin
dc.contributor.author
Fischer, Richard
dc.contributor.author
Fenchel, Klaus
dc.contributor.author
Haen, Sebastian
dc.contributor.author
Heukamp, Lukas
dc.contributor.author
Schulz, Christian
dc.contributor.author
Griesinger, Frank
dc.date.accessioned
2021-05-12T12:16:16Z
dc.date.available
2021-05-12T12:16:16Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/30580
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-30320
dc.description.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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
brain metastases
en
dc.subject
early access program
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1177/1758835920980558
dcterms.bibliographicCitation.journaltitle
Therapeutic Advances in Medical Oncology
dcterms.bibliographicCitation.originalpublishername
SAGE Publications
dcterms.bibliographicCitation.pagestart
1
dcterms.bibliographicCitation.pageend
15
dcterms.bibliographicCitation.volume
13
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33613692
dcterms.isPartOf.issn
1758-8340
dcterms.isPartOf.eissn
1758-8359