Abstract 1349P
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 Expanded Access Program (EAP) for advanced ROS1+ NSCLC after failure of at least one ALK-TKI. The data regarding efficacy and safety of lorlatinib in the context of pretreated ROS1+ NSCLC are lacking despite the recent publication of phase I-II trial.
Methods
Here we report the analysis of consecutive patients with advanced, refractory, ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to June 2019. Data were reviewed and collected from medical records. Primary endpoint was progression-free survival (PFS).
Results
Seventy-one patients were included: 41 (57.7%) women, 42 (60%) never-smokers, and 60 (84.5%) patients with stage IV disease at diagnosis. The most frequent histology was adenocarcinoma (94.2%). Median age was 59.3 years. At the time of initiation of lorlatinib, 45 (63.4%) patients had central nervous system (CNS) disease and 49 (79%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in respectively 31%/26.8%/16.9%/25.4% of patients. Forty-seven (66.2%) patients were previously treated with chemotherapy, 71 (100%) with crizotinib, 14 (19.7%) with a 2nd generation ALK-TKI. Median of follow-up was 14.8 months (95%CI, 12.5-25.7). Median PFS and median overall survival from the initiation of lorlatinib were 7.6 months (95%CI, 6.18-10.05) and 20.7 months (95%CI, 12.25-27.46) respectively. Median lorlatinib duration was 7.4 months (range: [0.5-34.7]). Overall response rate (ORR) and disease control were 45.5% (95%CI, 33.4% - 57.5%) and 84.8% (95%CI, 76.2% - 93.5%) respectively. CNS ORR was 41.8% (95%CI, 30.0% - 53.6%). 44 (62%) patients experienced tumor progression. Treatment was stopped for toxicity in 7 patients. The safety profile of lorlatinib was consistent with previously published data.
Conclusions
These real-life results confirmed lorlatinib as a major treatment option for patients with advanced ROS1+ NSCLC after failure of crizotinib.
Clinical trial identification
NCT03727477.
Editorial acknowledgement
Legal entity responsible for the study
IFCT.
Funding
Pfizer.
Disclosure
M. Duruisseaux: Advisory/Consultancy: Roche, BMS, AstraZeneca, MSD, Pfizer, AbbVie, Boehringer Ingelheim, Takeda; Research grant/Funding (institution): Nanostring, Blueprint, Pfizer, Takeda. J. Cadranel: Advisory/Consultancy: AZ BI BMS MSD Roche Pfizer Lilly Novartis Takeda. D. Moro-Sibilot: Honoraria (self): BMS MSD Lilly Takeda Novartis Pfizer Roche AbbVie Boehringer AstraZeneca. J. Bennouna: Honoraria (self): BMS AstraZeneca Boehringer Ingelheim Bayer Roche MSD Servier. G. Zalcman: Honoraria (self): Pfizer; Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: MSD. C. Ricordel: Research grant/Funding (institution): Roche. 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. V. Westeel: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Fresenius; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim. S. Baldacci: Travel/Accommodation/Expenses: Lilly GSK Roche Pfizer; Honoraria (self): MSD Boehringer Ingelheim; Research grant/Funding (institution): Merck. All other authors have declared no conflicts of interest.