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Ref Type Journal Article
PMID (33380260)
Authors Meng Z, Li T, Wang P, Lizaso A, Huang D
Title The efficacy of lorlatinib in a lung adenocarcinoma patient with a novel ALK G1202L mutation: a case report.
Abstract Text Acquired mutations in anaplastic lymphoma kinase (ALK) gene have been implicated as the major resistance mechanism to ALK inhibitors; however, information on the treatment options after acquiring novel ALK secondary mutations is limited. Herein, we report the efficacy of lorlatinib upon the detection of a novel ALK G1202L after progression on brigatinib. Our patient was a 30-year-old man with ALK-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 EML4-ALK fusion and the emergence of a novel ALK 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 ALK G1202L and can serve as an option for the clinical management of patients with ALK-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 ALK-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.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ALK G1202L missense unknown ALK G1202L lies within the protein kinase domain of the Alk protein ( G1202L has been identified in the scientific literature (PMID: 33380260), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2024).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK G1202L lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, treatment with Lorbrena (lorlatinib) resulted in stable disease with a progression-free survival of 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK G1202L, which was acquired after prior ALK inhibitor therapy (PMID: 33380260). 33380260