Abstract 1368P
Background
The third-generation ALK- and ROS1 inhibitor lorlatinib has demonstrated clinical efficacy in several trials. We here report on the results of the German early access program (EAP), providing scarce data in the real word setting.
Methods
Patients with documented treatment failure of all approved ALK/ROS1-specific therapies (or with resistance mutations not covered by approved inhibitors or with leptomeningeal disease) and at least one other systemic treatment for metastatic NSCLC could be enrolled from April 2017 until May 2019. Progression-free (PFS) and overall survival (OS) were calculated. Values are given as median (range or 95% CI, respectively).
Results
51 patients were analyzed (age 56.1 years (32-81), 54.9% female, 60.8% never smokers, 98% adenocarcinoma), 37 (72.5%) and 14 (27.5%) were ALK- and ROS1 positive, respectively. Molecular analyses for ALK/ROS1-resistances prior to lorlatinib were available for 24 patients (47.1%), of whom 10 (41.7%) displaying ALK-G1202R or ROS1-G2032R mutations. 36 patients (70.6%) had active brain metastases and 9 (17.6%) exhibited symptoms of leptomeningeal carcinomatosis. Median number of prior systemic therapies was 4 (1-9), 3 (1-4) of whom containing specific TKIs. 34 ALK-positive patients (91.9%) were pretreated with Alectinib. Median duration of treatment with lorlatinib was 10.6 months (6.5-12.8). After a follow-up time of 16.2 months (12.7-18.1) response rate, PFS, and time to treatment failure were 45.1% (n=23), 8.0 months (4.2-11.8), and 13.0 months (8.8-17.3). OS was 24.7 months (6.3-43.1), reaching 79.6 months (58.2-101.0) since primary diagnosis. G1202R/G2032R conferred a reduced PFS (4.1 vs. 11.0 months, p=0.04), whereas OS was neither influenced by resistance mutations, prior treatment with Alectinib (ALK-positive patients) nor brain metastases.
Conclusions
Our data from real life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients. Given the limits of a highly selected patient population, lorlatinib provides a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with brain metastases or leptomeningeal carcinomatosis.
Clinical trial identification
not applicable
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Frost: Advisory/Consultancy, outside the submitted work: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses, outside the submitted work: Bristol-Myers Squibb; Advisory/Consultancy, outside the submitted work: Boehringer Ingelheim; Advisory/Consultancy, outside the submitted work: MSD; Advisory/Consultancy, outside the submitted work: Takeda; Advisory/Consultancy, outside the submitted work: Roche Pharma; Advisory/Consultancy, outside the submitted work: Novartis; Honoraria (self), outside the submitted work: Berlin-Chemie; Advisory/Consultancy, outside the submitted work: Pfizer. J.A. Stratmann: Honoraria (self), outside the submitted work: Bristol-Myers Squibb; Honoraria (self), outside the submitted work: Novartis; Honoraria (self), outside the submitted work: Roche Pharma. J. Brinkmann: Spouse/Financial dependant, Employee: Pfizer. All other authors have declared no conflicts of interest.