The Efficacy of Lorlatinib in a Lung Adenocarcinoma Patient with a Novel ALK G1202L Mutation: a Case Report

Acquired mutations in anaplastic lymphoma kinase () gene have been implicated as the major resistance mechanism to ALK inhibitors; however, information on the treatment options after acquiring novel secondary mutations is limited. Herein, we report the efficacy of lorlatinib upon the detection of a novel G1202L after progression on brigatinib. Our patient was a 30-year-old man with -rearranged advanced lung adenocarcinoma. He had a partial clinical response to crizotinib lasting 11 months. Brigatinib was then administered for 12.8 months with stable disease as the best response. Sequencing at progression revealed the retention of fusion and the emergence of a novel G1202L mutation. With no standard treatment available, lorlatinib was administered, which achieved disease control for 9 months. Our report reveals the efficacy of lorlatinib in targeting G1202L and can serve as an option for the clinical management of patients with -rearranged lung adenocarcinoma after acquiring G1202L-mediated resistance from prior ALK inhibitor therapy. Furthermore, we also demonstrate the sequential use of crizotinib, brigatinib, and lorlatinib in a patient with advanced -rearranged lung adenocarcinoma with an overall progression-free survival of 33.3 months for the sequential ALK inhibitor regimens. His overall survival was 41.5 months inclusive of all regimens.