Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations

• Verfasst von: Frost, Nikolaj [VerfasserIn]
• Verfasst von: Christopoulos, Petros [VerfasserIn]
• Verfasst von: Kauffmann-Guerrero, Diego [VerfasserIn]
• Verfasst von: Stratmann, Jan [VerfasserIn]
• Verfasst von: Riedel, Richard [VerfasserIn]
• Verfasst von: Schaefer, Monica [VerfasserIn]
• Verfasst von: Alt, Jürgen [VerfasserIn]
• Verfasst von: Gütz, Sylvia [VerfasserIn]
• Verfasst von: Christoph, Daniel C. [VerfasserIn]
• Verfasst von: Laack, Eckart [VerfasserIn]
• Verfasst von: Faehling, Martin [VerfasserIn]
• Verfasst von: Fischer, Richard [VerfasserIn]
• Verfasst von: Fenchel, Klaus [VerfasserIn]
• Verfasst von: Haen, Sebastian P. [VerfasserIn]
• Verfasst von: Heukamp, Lukas [VerfasserIn]
• Verfasst von: Schulz, Christian [VerfasserIn]
• Verfasst von: Griesinger, Frank [VerfasserIn]
• Titel: Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations
• Titelzusatz: results from the German early access program
• Verf.angabe: 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
• E-Jahr: 2021
• Jahr: February 9, 2021
• Umfang: 15 S.
• Teil: volume:13
• Teil: year:2021
• Teil: month:01
• Teil: elocationid:1758835920980558
• Teil: pages:1-15
• Teil: extent:15
• Fussnoten: Gesehen am 13.04.2021
• Titel Quelle: Enthalten in: Therapeutic advances in medical oncology
• Ort Quelle: Thousand Oaks, Calif. : Sage, 2009
• Jahr Quelle: 2021
• Band/Heft Quelle: 13(2021) vom: Jan., Artikel-ID 1758835920980558, Seite 1-15
• ISSN Quelle: 1758-8359
• DOI: doi:10.1177/1758835920980558
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ALK
• Sach-SW: brain metastases
• Sach-SW: early access program
• Sach-SW: lorlatinib
• Sach-SW: NSCLC
• Sach-SW: ROS1
• Sach-SW: TP53
• K10plus-PPN: 1753963699

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.