Reference Detail

Ref Type

PMID

(35328235)

Authors

Catino A, Lacalamita R, De Summa S, Pesola F, Tommasi S, Galetta D

Title

Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung Adenocarcinoma: A Case Report.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Diagnostics (Basel, Switzerland)	12	3	2022 Mar 11		Diagnostics (Basel)

URL

Abstract Text

Second and third-generation ALK-TKI inhibitors have showed better activity and have replaced crizotinib in most of cases of advanced ALK-rearranged lung adenocarcinoma. The emergence of resistance adversely affects also the activity of these newer drugs; in particular, lorlatinib often shows multiple and complex resistance mechanisms. The case reported here highlights the importance of reassessing the biomolecular profile during the disease course, both by tissutal and liquid biopsy, with the aim of improving the knowledge of these resistance mechanisms, and so identifying new drugs or sequences able to optimize the management of these patients.

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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

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK G1202R	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) after the disease progressed on Alecensa (alectinib) treatment (PMID: 35328235).	35328235
EML4 - ALK ALK T1151K ALK G1202R ALK S1206F	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK S1206F and ALK T1151K were identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R after the disease progressed on Lorbrena (lorlatinib) treatment (PMID: 35328235).	35328235
EML4 - ALK ALK G1202R	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R (PMID: 35328235).	35328235