Molecular determinants of response to lorlatinib have not been established, but preclinical data suggest that ALK resistance mutations may represent a biomarker of response in previously treated patients.
Baseline plasma and tumor tissue samples were collected from 198 patients with ALK-positive non–small-cell lung cancer from the registrational phase II study of lorlatinib. We analyzed plasma DNA for ALK mutations using Guardant360. Tumor tissue DNA was analyzed using an ALK mutation–focused next-generation sequencing assay. Objective response rate, duration of response, and progression-free survival were evaluated according to ALK mutation status.
We concluded that in patients who have failed 1 or more second-generation ALK TKIs, lorlatinib shows greater efficacy in patients with ALK mutations compared with patients without ALK mutations. Tumor genotyping for ALK mutations after failure of a second-generation TKI may identify patients who are more likely to derive clinical benefit from lorlatinib. READ ARTICLE
Journal of Clinical Oncology DOI:10.1200/JCO.18.02236
Authors: Alice T. Shaw, Benjamin J. Solomon, Benjamin Besse, Todd M. Bauer, Chia-Chi Lin, Ross A. Soo, Gregory J. Riely, Sai-Hong Ignatius Ou, Jill S. Clancy, Sherry Li, Antonello Abbattista, Holger Thurm, Miyako Satouchi, D. Ross Camidge, Steven Kao, Rita Chiari, Shirish M. Gadgeel, Enriqueta Felip, Jean-François Martini