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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 9, 2021
|
| 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
|
| 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1753963699 | ||
| 003 | DE-627 | ||
| 005 | 20230426175801.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210413s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1177/1758835920980558 |2 doi | |
| 035 | |a (DE-627)1753963699 | ||
| 035 | |a (DE-599)KXP1753963699 | ||
| 035 | |a (OCoLC)1341404135 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Frost, Nikolaj |e VerfasserIn |0 (DE-588)1231302100 |0 (DE-627)1753965195 |4 aut | |
| 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 |
| 264 | 1 | |c February 9, 2021 | |
| 300 | |a 15 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 13.04.2021 | ||
| 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 | |
| 700 | 1 | |a Christopoulos, Petros |d 1977- |e VerfasserIn |0 (DE-588)138659702 |0 (DE-627)604886756 |0 (DE-576)308488067 |4 aut | |
| 700 | 1 | |a Kauffmann-Guerrero, Diego |e VerfasserIn |4 aut | |
| 700 | 1 | |a Stratmann, Jan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Riedel, Richard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schaefer, Monica |e VerfasserIn |4 aut | |
| 700 | 1 | |a Alt, Jürgen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gütz, Sylvia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Christoph, Daniel C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Laack, Eckart |e VerfasserIn |4 aut | |
| 700 | 1 | |a Faehling, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fischer, Richard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fenchel, Klaus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Haen, Sebastian P. |d 1979-2020 |e VerfasserIn |0 (DE-588)133231348 |0 (DE-627)539303259 |0 (DE-576)271826266 |4 aut | |
| 700 | 1 | |a Heukamp, Lukas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schulz, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Griesinger, Frank |e VerfasserIn |0 (DE-588)1080408916 |0 (DE-627)844436305 |0 (DE-576)453541747 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Therapeutic advances in medical oncology |d Thousand Oaks, Calif. : Sage, 2009 |g 13(2021) vom: Jan., Artikel-ID 1758835920980558, Seite 1-15 |h Online-Ressource |w (DE-627)604082282 |w (DE-600)2503443-1 |w (DE-576)308904494 |x 1758-8359 |7 nnas |a Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations results from the German early access program |
| 773 | 1 | 8 | |g volume:13 |g year:2021 |g month:01 |g elocationid:1758835920980558 |g pages:1-15 |g extent:15 |a Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations results from the German early access program |
| 856 | 4 | 0 | |u https://doi.org/10.1177/1758835920980558 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210413 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 138659702 |a Christopoulos, Petros |m 138659702:Christopoulos, Petros |d 910000 |d 950000 |d 950900 |d 50000 |e 910000PC138659702 |e 950000PC138659702 |e 950900PC138659702 |e 50000PC138659702 |k 0/910000/ |k 1/910000/950000/ |k 2/910000/950000/950900/ |k 0/50000/ |p 2 | ||
| 999 | |a KXP-PPN1753963699 |e 3906797279 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"eki":["1753963699"],"doi":["10.1177/1758835920980558"]},"recId":"1753963699","physDesc":[{"extent":"15 S."}],"title":[{"title":"Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations","subtitle":"results from the German early access program","title_sort":"Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations"}],"origin":[{"dateIssuedKey":"2021","dateIssuedDisp":"February 9, 2021"}],"person":[{"family":"Frost","given":"Nikolaj","role":"aut","display":"Frost, Nikolaj"},{"family":"Christopoulos","given":"Petros","role":"aut","display":"Christopoulos, Petros"},{"role":"aut","given":"Diego","display":"Kauffmann-Guerrero, Diego","family":"Kauffmann-Guerrero"},{"given":"Jan","role":"aut","display":"Stratmann, Jan","family":"Stratmann"},{"given":"Richard","role":"aut","display":"Riedel, Richard","family":"Riedel"},{"display":"Schaefer, Monica","given":"Monica","role":"aut","family":"Schaefer"},{"family":"Alt","given":"Jürgen","role":"aut","display":"Alt, Jürgen"},{"display":"Gütz, Sylvia","given":"Sylvia","role":"aut","family":"Gütz"},{"family":"Christoph","display":"Christoph, Daniel C.","given":"Daniel C.","role":"aut"},{"given":"Eckart","role":"aut","display":"Laack, Eckart","family":"Laack"},{"display":"Faehling, Martin","role":"aut","given":"Martin","family":"Faehling"},{"display":"Fischer, Richard","role":"aut","given":"Richard","family":"Fischer"},{"given":"Klaus","role":"aut","display":"Fenchel, Klaus","family":"Fenchel"},{"family":"Haen","given":"Sebastian P.","role":"aut","display":"Haen, Sebastian P."},{"family":"Heukamp","display":"Heukamp, Lukas","role":"aut","given":"Lukas"},{"display":"Schulz, Christian","role":"aut","given":"Christian","family":"Schulz"},{"family":"Griesinger","display":"Griesinger, Frank","role":"aut","given":"Frank"}],"name":{"displayForm":["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"]},"note":["Gesehen am 13.04.2021"],"relHost":[{"language":["eng"],"pubHistory":["1.2009 -"],"part":{"text":"13(2021) vom: Jan., Artikel-ID 1758835920980558, Seite 1-15","extent":"15","year":"2021","volume":"13","pages":"1-15"},"note":["Gesehen am 15.03.2012"],"type":{"bibl":"periodical","media":"Online-Ressource"},"origin":[{"publisher":"Sage","dateIssuedKey":"2009","dateIssuedDisp":"2009-","publisherPlace":"Thousand Oaks, Calif."}],"id":{"zdb":["2503443-1"],"eki":["604082282"],"issn":["1758-8359"]},"recId":"604082282","disp":"Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations results from the German early access programTherapeutic advances in medical oncology","physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"Therapeutic advances in medical oncology","title":"Therapeutic advances in medical oncology"}]}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"]} | ||
| SRT | |a FROSTNIKOLLORLATINIB9202 | ||