Lorlatinib for advanced anaplastic lymphoma kinase–positive non–small cell lung cancer: Results of the IFCT-1803 LORLATU cohort - Archive ouverte HAL
Journal Articles European Journal of Cancer Year : 2022

Lorlatinib for advanced anaplastic lymphoma kinase–positive non–small cell lung cancer: Results of the IFCT-1803 LORLATU cohort

1 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
2 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
3 IGR - Institut Gustave Roussy
4 Université Paris-Saclay
5 Centre Léon Bérard [Lyon]
6 Nouvel Hôpital Civil de Strasbourg
7 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
10 Hôpital Morvan [Brest]
11 Hôpital Foch [Suresnes]
12 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
13 ICM - Institut régional de Cancérologie de Montpellier
14 UCBL - Université Claude Bernard Lyon 1
15 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
16 Hôpital Louis Pradel [CHU - HCL]
17 CHI Créteil
18 Hôpital Michallon
19 CHU Tenon [AP-HP]
20 GRC 4 - Theranoscan - Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules
21 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
22 CRAN - Centre de Recherche en Automatique de Nancy
23 Institut Bergonié [Bordeaux]
24 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
25 CHU Gabriel Montpied [Clermont-Ferrand]
26 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
27 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
28 CHCB - Centre Hospitalier de la Côte Basque
29 IODE - Institut de l'Ouest : Droit et Europe
30 IFCT - Intergroupe Francophone de Cancérologie Thoracique [Paris]
31 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
32 Institut Curie [Paris]
Isabelle Monnet
  • Function : Author

Abstract

Background: Anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) represents a rare subset of lung cancer, with specific presentation, and multiple treatment options, including selective tyrosine kinase inhibitors (TKIs). Real-world evidence is insufficient regarding the actual real-life treatment sequences in the late line setting, and available clinical trials may not reflect real-world situation. Here, we took advantage of the French Expanded Access Program (EAP) of lorlatinib, a third-generation TKI targeting ALK and ROS1, to assess treatment sequencing, and lorlatinib efficacy and safety, in patients with ALK+ NSCLC.Methods: All consecutive patients with advanced ALK+ NSCLC treated between October 2015 and June 2019 with lorlatinib as part of EAP were included. Data were collected and reviewed from medical records by independent research staff of the French Thoracic Cancer Intergroup. The primary endpoint was progression-free survival (PFS).Results: Of the 208 patients included, 117 (56%) were female, 142 (69%) were never smokers, and 180 (87%) had stage IV NSCLC at diagnosis. The most frequent histology was adenocarcinoma (94%), and the median age was 60.9 years. At the time of lorlatinib initiation, 160 (77%) patients had brain metastases, and 125 (72%) were performance status 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 4%/17%/30%/49% of patients. A total of 162 (78%) patients had previously been treated with chemotherapy, 194 (93%) with a first-generation ALK-TKI, 195 (94%) with a second-generation ALK-TKI. The median follow-up from lorlatinib initiation was 23.3 months. The median PFS, median overall survival (OS) from lorlatinib initiation and median OS from advanced NSCLC diagnosis were 9.9 months (95% confidence interval [CI] 6-12.3 months), 32.9 months (95% CI 18.7 months to not reached) and 97.3 months (95% CI 75.7-152.8 months), respectively. The median duration of treatment with lorlatinib was 11.8 months (95% CI 8.5-18.8 months). Overall response and disease control rate were 49% and 86%, respectively. Central nervous system objective response rate was 56%. Treatment was stopped due to toxicity in 28 patients (14%). The safety profile of lorlatinib was consistent with previously published data.Conclusions: Real-world evidence indicates that lorlatinib offers a significant clinical benefit and high intracerebral antitumour activity in heavily pretreated patients with ALK+ NSCLC.

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Cancer
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hal-04728569 , version 1 (13-11-2024)

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Simon Baldacci, Benjamin Besse, Virginie Avrillon, Bertrand Mennecier, Julien Mazieres, et al.. Lorlatinib for advanced anaplastic lymphoma kinase–positive non–small cell lung cancer: Results of the IFCT-1803 LORLATU cohort. European Journal of Cancer, 2022, 166, pp.51-59. ⟨10.1016/j.ejca.2022.01.018⟩. ⟨hal-04728569⟩
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