EML4-ALK: Update on ALK Inhibitors

被引：2

作者：

Bearz, Alessandra ^{[1
]}

Bertoli, Elisa ^{[1
]}

Stanzione, Brigida ^{[2
]}

De Carlo, Elisa ^{[2
]}

Del Conte, Alessandro ^{[1
]}

Bortolot, Martina ^{[2
,3
]}

Torresan, Sara ^{[2
,3
]}

Berto, Eleonora ^{[2
]}

Da Ros, Valentina ^{[2
]}

Pelin, Giulia Maria ^{[1
]}

Fassetta, Kelly ^{[2
]}

Rossetto, Silvia ^{[1
]}

Spina, Michele ^{[2
]}

机构：

[1] IRCCS, Ctr Riferimento Oncol Aviano CRO, NCI, I-33081 Aviano, Italy

[2] IRCCS, Ctr Riferimento Oncol Aviano CRO, Dept Med Oncol, I-33081 Aviano, Italy

[3] Univ Udine, Dept Med, I-33100 Udine, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2025年 / 26卷 / 01期

关键词：

lung cancer; NSCLC; EMLA4-ALK; TKI; CELL LUNG-CANCER; CIRCULATING TUMOR DNA; LYMPHOMA KINASE ALK; PRECISION MEDICINE; TREATMENT-NAIVE; POSITIVE NSCLC; FUSION GENE; OPEN-LABEL; CRIZOTINIB; EFFICACY;

D O I：

10.3390/ijms26010308

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Since the discovery of the first-generation ALK inhibitor, many other tyrosine kinase inhibitors have been demonstrated to be effective in the first line or further lines of treatment in patients with advanced non-small cell lung cancer with EMLA4-ALK translocation. This review traces the main milestones in the treatment of ALK-positive metastatic patients and the survival outcomes in the first-line and second-line settings with different ALK inhibitors. It presents the two options available for first-line treatment at the present time: sequencing different ALK inhibitors versus using the most potent inhibitor in front-line treatment. The efficacy outcomes of different ALK inhibitors in the first-line setting; the molecular profile of the disease, including mutation resistances and ALK variants and co-mutations; and patients' co-morbidities and inhibitor toxicities should be taken into account to address the choice of the first-line treatment, as suggested in this review.

引用

页数：13

共 56 条

[1] Efficacy of Lorlatinib in Treatment-Naive Patients With ALK-Positive Advanced NSCLC in Relation to EML4::ALK Variant Type and ALK With or Without TP53 Mutations [J].

Bearz, Alessandra ;

Martini, Jean-Francois ;

Jassem, Jacek ;

Kim, Sang-We ;

Chang, Gee-Chen ;

Shaw, Alice T. ;

Shepard, Deborah A. ;

Dall'O, Elisa ;

Polli, Anna ;

Thurm, Holger ;

Zalcman, Gerard ;

Campelo, Maria Rosario Garcia ;

Penkov, Konstantin ;

Hayashi, Hidetoshi ;

Solomon, Benjamin J. .

JOURNAL OF THORACIC ONCOLOGY, 2023, 18 (11) :1581-1593

[2] Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial [J].

Camidge, D. Ross ;

Kim, Hye Ryun ;

Ahn, Myung-Ju ;

Yang, James C. H. ;

Han, Ji-Youn ;

Hochmair, Maximilian J. ;

Lee, Ki Hyeong ;

Delmonte, Angelo ;

Campelo, Maria Rosario Garcia ;

Kim, Dong-Wan ;

Griesinger, Frank ;

Felip, Enriqueta ;

Califano, Raffaele ;

Spira, Alexander I. ;

Gettinger, Scott N. ;

Tiseo, Marcello ;

Lin, Huamao M. ;

Liu, Yuyin ;

Vranceanu, Florin ;

Niu, Huifeng ;

Zhang, Pingkuan ;

Popat, Sanjay .

JOURNAL OF THORACIC ONCOLOGY, 2021, 16 (12) :2091-2108

[3] Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial [J].

Camidge, D. Ross ;

Kim, Hye Ryun ;

Ahn, Myung-Ju ;

Yang, James C. H. ;

Han, Ji-Youn ;

Hochmair, Maximilian J. ;

Lee, Ki Hyeong ;

Delmonte, Angelo ;

Garcia Campelo, Maria Rosario ;

Kim, Dong-Wan ;

Griesinger, Frank ;

Felip, Enriqueta ;

Califano, Raffaele ;

Spira, Alexander ;

Gettinger, Scott N. ;

Tiseo, Marcello ;

Lin, Huamao M. ;

Gupta, Neeraj ;

Hanley, Michael J. ;

Ni, Quanhong ;

Zhang, Pingkuan ;

Popat, Sanjay .

JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (31) :3592-+

[4] Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non-Small Cell Lung Cancer in the Global Phase III ALEX Study [J].

Camidge, D. Ross ;

Dziadziuszko, Rafal ;

Peters, Solange ;

Mok, Tony ;

Noe, Johannes ;

Nowicka, Malgorzata ;

Gadgeel, Shirish M. ;

Cheema, Parneet ;

Pavlakis, Nick ;

de Marinis, Filippo ;

Cho, Byoung Chul ;

Zhang, Li ;

Moro-Sibilot, Denis ;

Liu, Ting ;

Bordogna, Walter ;

Balas, Bogdana ;

Mueller, Barbara ;

Shaw, Alice T. .

JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (07) :1233-1243

[5] ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges [J].

Chow, Laura Q. M. ;

Barlesi, Fabrice ;

Bertino, Erin M. ;

van den Bent, Martin J. ;

Wakelee, Heather A. ;

Wen, Patrick Y. ;

Chiu, Chao-Hua ;

Orlov, Sergey ;

Chiari, Rita ;

Majem, Margarita ;

McKeage, Mark ;

Yu, Chong-Jen ;

Garrido, Pilar ;

Hurtado, Felipe K. ;

Arratia, Pilar Cazorla ;

Song, Yuanbo ;

Branle, Fabrice ;

Shi, Michael ;

Kim, Dong-Wan .

CLINICAL CANCER RESEARCH, 2022, 28 (12) :2506-2516

[6] EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated metastatic spread, early treatment failure and worse overall survival in ALK+ non-small cell lung cancer [J].

Christopoulos, Petros ;

Endris, Volker ;

Bozorgmehr, Farastuk ;

Elsayed, Mei ;

Kirchner, Martina ;

Ristau, Jonas ;

Buchhalter, Ivo ;

Penzel, Roland ;

Herth, Felix J. ;

Heussel, Claus P. ;

Eichhorn, Martin ;

Muley, Thomas ;

Meister, Michael ;

Fischer, Juergen R. ;

Rieken, Stefan ;

Warth, Arne ;

Bischoff, Helge ;

Schirmacher, Peter ;

Stenzinger, Albrecht ;

Thomas, Michael .

INTERNATIONAL JOURNAL OF CANCER, 2018, 142 (12) :2589-2598

[7] Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases [J].

Costa, Daniel B. ;

Shaw, Alice T. ;

Ou, Sai-Hong I. ;

Solomon, Benjamin J. ;

Riely, Gregory J. ;

Ahn, Myung-Ju ;

Zhou, Caicun ;

Shreeve, S. Martin ;

Selaru, Paulina ;

Polli, Anna ;

Schnell, Patrick ;

Wilner, Keith D. ;

Wiltshire, Robin ;

Camidge, D. Ross ;

Crino, Lucio .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (17) :1881-1888

[8] CSF Concentration of the Anaplastic Lymphoma Kinase Inhibitor Crizotinib [J].

Costa, Daniel B. ;

Kobayashi, Susumu ;

Pandya, Shuchi S. ;

Yeo, Wee-Lee ;

Shen, Zhongzhou ;

Tan, Weiwei ;

Wilner, Keith D. .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (15) :E443-E445

[9] Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal-Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK) [J].

Cui, J. Jean ;

Tran-Dube, Michelle ;

Shen, Hong ;

Nambu, Mitchell ;

Kung, Pei-Pei ;

Pairish, Mason ;

Jia, Lei ;

Meng, Jerry ;

Funk, Lee ;

Botrous, Iriny ;

McTigue, Michele ;

Grodsky, Neil ;

Ryan, Kevin ;

Padrique, Ellen ;

Alton, Gordon ;

Timofeevski, Sergei ;

Yamazaki, Shinji ;

Li, Quhua ;

Zou, Helen ;

Christensen, James ;

Mroczkowski, Barbara ;

Bender, Steve ;

Kania, Robert S. ;

Edwards, Martin P. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (18) :6342-6363

[10] Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity [J].

Dagogo-Jack, Ibiayi ;

Rooney, Marguerite ;

Lin, Jessica J. ;

Nagy, Rebecca J. ;

Yeap, Beow Y. ;

Hubbeling, Harper ;

Chin, Emily ;

Ackil, Jennifer ;

Farago, Anna F. ;

Hata, Aaron N. ;

Lennerz, Jochen K. ;

Gainor, Justin F. ;

Lanman, Richard B. ;

Shaw, Alice T. .

CLINICAL CANCER RESEARCH, 2019, 25 (22) :6662-6670

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