Abstract 1303P
Background
Lorlatinib is a third-generation tyrosine kinase inhibitor (TKI) targeting ALK and ROS1. Lorlatinib has been made available in France from October 2015 through an EAP for advanced ALK+ NSCLC after failure of at least one ALK-TKI. Data regarding efficacy and safety of lorlatinib used in various ALK-TKI sequences are lacking despite the results of the landmark multi-cohort phase II trial.
Methods
All consecutive patients with advanced refractory ALK+ NSCLC enrolled in the French lorlatinib EAP from October 2015 to June 2019 were included. Data were collected from medical records. Primary endpoint was progression-free survival (PFS).
Results
197 patients were included: 112 (56.9%) women, 134 (69.1%) never-smokers, and 170 (86.3%) patients with stage IV disease at diagnosis. The most frequent histology was adenocarcinoma (93.4%). Median age was 60.6 years. At the time of initiation of lorlatinib, characteristics were the following: 152 (77.2%) patients had central nervous system (CNS) disease, 121 (72.9%) were PS0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 4.1%/18.3%/29.4%/48.2% of patients. 152 (77.2%) patients were previously treated with chemotherapy, 182 (92.4%) with crizotinib, 183 (92.9%) with a 2nd generation ALK-TKI. Median of follow up from lorlatinib intiation was 17.1 months (95%CI, 15.9-19.3). Median PFS and median overall survival from lorlatinib initiation were 9.72 months (95%CI, 5.95-11.96) and 32.92 months (95%CI, 18.73-NR), respectively. Median lorlatinib duration was 7.5 months (range: [0.2-37.9]). Overall response rate (ORR) and disease control rate were 50.6% (95%CI, 43.3% - 57.9%) and 86.7% (95%CI, 81.7% - 91.6%) respectively. CNS ORR was 42.9% (95%CI, 35.8% - 50.1%). 100 (50.8%) patients experienced tumor progression on lorlatinib. Treatment was stopped for treatment-related toxicity in 28 patients. The safety profile of lorlatinib was consistent with previously published data.
Conclusions
These real-life results show that lorlatinib NSCLC provides significant clinical benefit as well as a central nervous system anti tumoral activity in heavily pre-treated advanced ALK+ patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IFCT.
Funding
Pfizer.
Disclosure
S. Baldacci: Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: GSK; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Merck. B. Besse: Research grant/Funding (institution): AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Ignyta, Ipsen, Inivata, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE Immunotherapeutics, Pfizer, PharmaMar. P. Dubray-Longeras: Research grant/Funding (institution): MSD. J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Hengrui; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Takeda. R. Descourt: Advisory/Consultancy: Takeda; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca. M. Duruisseaux: Advisory/Consultancy: Roche, BMS, AstraZeneca, MSD, Pfizer, AbbVie, Boehringer Ingelheim, Takeda; Research grant/Funding (institution): Nanostring, Blueprint, Pfizer, Takeda. X. Quantin: Travel/Accommodation/Expenses: Pfizer. D. Moro-Sibilot: Honoraria (self): BMS MSD Lilly Takeda Novartis Pfizer Roche AbbVie Boehringer AstraZeneca. V. Westeel: Speaker Bureau/Expert testimony: Roche, MSD, BMS; Honoraria (self): Roche; Advisory/Consultancy: BMS, AstraZeneca, Roche, Takeda; Research grant/Funding (institution): BMS, MSD, Roche, AbbVie, Merck Serono, Lilly, Fresenius; Travel/Accommodation/Expenses: Roche, Pfizer, BMS, Boehringer Ingelheim. All other authors have declared no conflicts of interest.