Universität zu Köln

Frost, Nikolaj ORCID: 0000-0001-7452-7129, Christopoulos, Petros ORCID: 0000-0002-7966-8980, Kauffmann-Guerrero, Diego, Stratmann, Jan, Riedel, Richard, Schaefer, Monica, Alt, Jurgen, Gutz, Sylvia, Christoph, Daniel C., Laack, Eckart, Faehling, Martin, Fischer, Richard, Fenchel, Klaus, Haen, Sebastian, Heukamp, Lukas, 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. Ther. Adv. Med. Oncol., 13. LONDON: SAGE PUBLICATIONS LTD. ISSN 1758-8359

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Frost, Nikolaj UNSPECIFIED orcid.org/0000-0001-7452-7129 UNSPECIFIED Christopoulos, Petros UNSPECIFIED orcid.org/0000-0002-7966-8980 UNSPECIFIED Kauffmann-Guerrero, Diego UNSPECIFIED UNSPECIFIED UNSPECIFIED Stratmann, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Riedel, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Alt, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutz, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Christoph, Daniel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Laack, Eckart UNSPECIFIED UNSPECIFIED UNSPECIFIED Faehling, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Fenchel, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Haen, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Griesinger, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-604556
DOI:	10.1177/1758835920980558
Journal or Publication Title:	Ther. Adv. Med. Oncol.
Volume:	13
Date:	2021
Publisher:	SAGE PUBLICATIONS LTD
Place of Publication:	LONDON
ISSN:	1758-8359
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLINICAL IMPACT; CRIZOTINIB; PROGRESSION; CHEMOTHERAPY; ALECTINIB; SURVIVAL; THERAPY; CNS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60455