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Review

Navigating resistance to ALK inhibitors in the lorlatinib era: a comprehensive perspective on NSCLC

, , , , , , & show all
Pages 347-361 | Received 19 Oct 2023, Accepted 15 Apr 2024, Published online: 21 Apr 2024

References

  • Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446–454. doi: 10.1038/nature25183
  • Shaw AT, Mino-Kenudson M. Targeting ALK in lung cancer: rationale, progress, and prospects. Nat Rev Clin Oncol. 2013;10(5):268–277.
  • Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncology. 2013;18(7):865–875. doi: 10.1634/theoncologist.2013-0095
  • Peters S, Zimmermann S, Adjei AA. METEG (MET exon 14 skipping alterations): a review of clinical and mechanistic data. Oncology. 2021;23(3):246–253.
  • Awad MM, Shaw AT. ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. H&O. 2014;12:429–39.
  • Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol. 2014;11(8):473–481. doi: 10.1038/nrclinonc.2014.104
  • Palmer RH, Vernersson E, Grabbe C, et al. Anaplastic lymphoma kinase: signalling in development and disease. Biochem J. 2009;420(3):345–361. doi: 10.1042/BJ20090387
  • Hurley SP, Clary DO, Copie V, et al. Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system. J Comp Neurol. 2006;495(2):202–212. doi: 10.1002/cne.20887
  • Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–1134. doi: 10.1016/j.cell.2010.06.011
  • Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, npm, in non-hodgkin’s lymphoma. Science. 1994;263:1281–1284. doi: 10.1126/science.8122112
  • Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131(6):1190–1203. doi: 10.1016/j.cell.2007.11.025
  • Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non–small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27(26):4247–4253. doi: 10.1200/JCO.2009.22.6993
  • Selinger CI, Rogers TM, Russell PA, et al. Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization. Mod Pathol. 2013;26(12):1545–1553. doi: 10.1038/modpathol.2013.87
  • Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998–2006. doi: 10.1001/jama.2014.3741
  • Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–2177. doi: 10.1056/NEJMoa1408440
  • Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-Mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018;36(22):2251–2258. doi: 10.1200/JCO.2017.77.4794
  • Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–929. doi: 10.1016/S0140-6736(17)30123-X
  • Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017;18(7):874–886. doi: 10.1016/S1470-2045(17)30339-X
  • Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-Positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829–838. doi: 10.1056/NEJMoa1704795
  • Hida T, Nokihara H, Kim YH, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390(10089):29–39. doi: 10.1016/S0140-6736(17)30565-2
  • Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056–1064. doi: 10.1016/j.annonc.2020.04.478
  • Hotta K, Hida T, Nokihara H, et al. Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer. ESMO Open. 2022;7(4):100527. doi: 10.1016/j.esmoop.2022.100527
  • Gadgeel S, Peters S, Mok T, et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018;29(11):2214–2222. doi: 10.1093/annonc/mdy405
  • Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379(21):2027–2039. doi: 10.1056/NEJMoa1810171
  • Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor-naive advanced ALK-Positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):2091–2108. doi: 10.1016/j.jtho.2021.07.035
  • Lovly CM, Heuckmann JM, de Stanchina E, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011;71(14):4920–4931. doi: 10.1158/0008-5472.CAN-10-3879
  • Horn L, Infante JR, Reckamp KL, et al. Ensartinib (X-396) in ALK-Positive non-small cell lung cancer: results from a first-in-human phase i/ii, multicenter study. Clin Cancer Res. 2018;24(12):2771–2779. doi: 10.1158/1078-0432.CCR-17-2398
  • Horn L, Wang Z, Wu G, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol. 2021;7(11):1617–1625. doi: 10.1001/jamaoncol.2021.3523
  • Shaw A, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18(12):1590–1599. doi: 10.1016/S1470-2045(17)30680-0
  • Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654–1667. doi: 10.1016/S1470-2045(18)30649-1
  • Shaw AT, Bauer TM, de Marinis F, et al. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020;383(21):2018–2029. doi: 10.1056/NEJMoa2027187
  • Felip E, Shaw AT, Bearz A, et al. Intracranial and extracranial efficacy of lorlatinib in patients with ALK-positive non-small-cell lung cancer previously treated with second-generation ALK TKIs. Ann Oncol. 2021;32(5):620–630. doi: 10.1016/j.annonc.2021.02.012
  • Dagogo-Jack I, Oxnard GR, Evangelist M, et al. Phase II study of lorlatinib in patients with anaplastic lymphoma kinase–positive lung cancer and CNS-specific relapse. JCO Precis Oncol. 2022;e2100522(6). doi: 10.1200/PO.21.00522
  • Solomon BJ, Bauer TM, Ou SH I, et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non-small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022;40(31):3593–3602. doi: 10.1200/JCO.21.02278
  • Isozaki H, Takigawa N, Kiura K. Mechanisms of acquired resistance to ALK inhibitors and the rationale for treating ALK-positive lung cancer. Cancers (Basel). 2015;7(2):763–783. doi: 10.3390/cancers7020763
  • Hendriks LE, Kerr KM, Menis J, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):339–357. doi: 10.1016/j.annonc.2022.12.009
  • Volckmar AL, Sültmann H, Riediger A, et al. A field guide for cancer diagnostics using cell-free DNA: from principles to practice and clinical applications. Genes Chromosomes Cancer. 2018;57(3):123–139. doi: 10.1002/gcc.22517
  • Murtaza M, Dawson SJ, Tsui DWY, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497(7447):108–112. doi: 10.1038/nature12065
  • Schwarzenbach H, Nishida N, Calin GA. Clinical relevance of circulating cell-free microRnas in cancer. Nat Rev Clin Oncol. 2014;11(3):145–156. doi: 10.1038/nrclinonc.2014.5
  • Hiley C, de Bruin EC, McGranahan N, et al. Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine. Genome Biol. 2014;15(8):453. doi: 10.1186/s13059-014-0453-8
  • Tie J, Kinde I, Wang Y, et al. Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer. Ann Oncol. 2015;26(8):1715–1722. doi: 10.1093/annonc/mdv177
  • McCoach CE, Blakely CM, Banks KC, et al. Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung cancer. Clin Cancer Res. 2018;24(12):2758–2770. doi: 10.1158/1078-0432.CCR-17-2588
  • Xiaomeng Y, Yueyi L, Hang W, et al. Small cell lung cancer transformation: from pathogenesis to treatment. Semin Cancer Biol. 2022;86:595–606. doi: 10.1016/j.semcancer.2022.03.006
  • Coleman N, Wotherspoon A, Yousaf N, et al. Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib. Lung Cancer. 2019;134:117–120. doi: 10.1016/j.lungcan.2019.05.025
  • Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363(18):1734–1739. doi: 10.1056/NEJMoa1007478
  • Azam M, Seeliger MA, Gray NS, et al. Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol. 2008;15(10):1109–1118. doi: 10.1038/nsmb.1486
  • Zuccotto F, Ardini E, Casale E, et al. Through the “gatekeeper door”: exploiting the active kinase conformation. J Med Chem. 2010;53(7):2681–2694. doi: 10.1021/jm901443h
  • Sun HY, Ji F-Q. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK. Biochem Biophys Res Commun. 2012;423(2):319–324. doi:10.1016/j.bbrc.2012.05.120
  • Ceccon M, Mologni L, Bisson W, et al. Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated alk inhibitors. Mol Cancer Res. 2013;11(2):122–132. doi: 10.1158/1541-7786.MCR-12-0569
  • Yu Y, Ou Q, Wu X, et al. Concomitant resistance mechanisms to multiple tyrosine kinaseinhibitors in ALK-positive non- small cell lung cancer. Lung Cancer. 2018;127:19–24. doi: 10.1016/j.lungcan.2018.11.024
  • Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014;4(6):662–673. doi: 10.1158/2159-8290.CD-13-0846
  • Ou SH, Azada M, Hsiang DJ, et al. Next-generation sequencing reveals a novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib. J Thorac Oncol. 2014;9(4):549–553. doi: 10.1097/JTO.0000000000000094
  • Fontana D, Ceccon M, Gambacorti-Passerini C, et al. Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK. Cancer Med. 2015;4(7):953–965. doi:10.1002/cam4.413
  • Ceccon M, Mologni L, Giudici G, et al. Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma. Mol Cancer Res. 2015;13(4):775–783. doi: 10.1158/1541-7786.MCR-14-0157
  • Noé J, Lovejoy A, Ou SH, et al. ALK mutation status before and after alectinib treatment in locally advanced or metastatic ALK-positive NSCLC: pooled analysis of two prospective trials. J Thorac Oncol. 2020;15(4):601–608. doi: 10.1016/j.jtho.2019.10.015
  • Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-Rearranged lung cancer. Cancer Discov. 2016;6(10):1118–1133. doi: 10.1158/2159-8290.CD-16-0596
  • Shaw AT, Engelman JA, Leshchiner I. Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med. 2016;374(1):1790–1791. doi:10.1056/NEJMoa1508887
  • Yang Y, Huang J, Wang T, et al. Decoding the evolutionary response to ensartinib in patients with ALK-Positive NSCLC by dynamic circulating tumor DNA sequencing. J Thorac Oncol. 2021;16(5):827–839. doi: 10.1016/j.jtho.2021.01.1615
  • Zou HY, Friboulet L, Kodack DP, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 2015;28(1):70–81. doi: 10.1016/j.ccell.2015.05.010
  • Shaw AT, Solomon BJ, Besse B, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 2019;37(16):1370–1379. doi: 10.1200/JCO.18.02236
  • Shaw AT, Friboulet L, Leshchiner I, et al. Resensitization to Crizotinib by the lorlatinib ALK resistance mutation L1198F. N Engl J Med. 2016;374(1):54–61. doi: 10.1056/NEJMoa1508887
  • Yoda S, Lin JJ, Lawrence MS, et al. Sequential ALK inhibitors can select for lorlatinib-resistant compound ALK mutations in ALK-Positive lung cancer. Cancer Discov. 2018;8(6):714–729. doi: 10.1158/2159-8290.CD-17-1256
  • Shiba-Ishii A, Johnson TW, Dagogo-Jack I, et al. Sequential ALKinhibitors can select for lorlatinib-resistant compound ALK mutations in ALK-positive lung cancer. Nat Cancer. 2022;3(6):710–722. doi: 10.1038/s43018-022-00399-6
  • Takahashi K, Seto Y, Okada K, et al. Overcoming resistance by ALK compound mutation (I1171S + G1269A) after sequential treatment of multiple ALK inhibitors in non- small cell lung cancer. Thorac Cancer. 2020;11(3):581–587. doi: 10.1111/1759-7714.13299
  • Recondo G, Mezquita L, Facchinetti F, et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-Rearranged lung cancer. Clin Cancer Res. 2020;26(1):242–255. doi: 10.1158/1078-0432.CCR-19-1104
  • Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-Positive lung cancer. J Clin Oncol. 2018;36(12):1199–1206. doi: 10.1200/JCO.2017.76.2294
  • Tabbò F, Muscarella LA, Gobbini E, et al. Detection of ALK fusion variants by RNA-based NGS and clinical outcome correlation in NSCLC patients treated with ALK-TKI sequences. Eur J Cancer. 2022;174:200–211. doi: 10.1016/j.ejca.2022.07.026
  • Bearz A, Martini JF, Jassem J, et al. Efficacy of lorlatinib in treatment-naive patients with ALK-positive advanced non- small cell lung cancer in relation to EML4: ALK variant type and ALK with or without TP53 mutations. Journal Of Thor Oncol. 2023;18(11):1581–1593. doi: 10.1016/j.jtho.2023.07.023
  • Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):120ra17. doi: 10.1126/scitranslmed.3003316
  • Doebele R, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472–1482. doi: 10.1158/1078-0432.CCR-11-2906
  • Wilson FH, Johannessen CM, Piccioni F, et al. A functional landscape of resistance to ALK inhibition in lung cancer. Cancer Cell. 2015;27(3):397–408. doi: 10.1016/j.ccell.2015.02.005
  • Miyawaki M, Yasuda H, Tani T, et al. Overcoming EGFR bypass signal-induced acquired resistance to ALK tyrosine kinase inhibitors in ALK-Translocated lung cancer. Mol Cancer Res. 2017;15(1):106–114. doi: 10.1158/1541-7786.MCR-16-0211
  • Crystal AS, Shaw AT, Sequist LV, et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science. 2014;346(6216):1480–1486. doi: 10.1126/science.1254721
  • Dagogo-Jack I, Yoda S, Lennerz JK, et al. Met alterations are a recurring and actionable resistance mechanism in ALK-positive lung cancer. Clin Cancer Res. 2020;26(11):2535–2545. doi: 10.1158/1078-0432.CCR-19-3906
  • Ryul Kim H, Kim WS, Choi YJ, et al. Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation. Mol Oncol. 2013;7(6):1093–1102. doi: 10.1016/j.molonc.2013.08.001
  • Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75–90. doi: 10.1016/j.bbcan.2009.03.002
  • Takegawa N, Hayashi H, Iizuka N, et al. Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. Ann Oncol. 2016;27(5):953–955. doi: 10.1093/annonc/mdw032
  • Miyamoto S, Ikushima S, Ono R, et al. Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib. Jpn J Clin Oncol. 2016;46(2):170–173. doi: 10.1093/jjco/hyv173
  • Fujita S, Masago K, Katakami N, et al. Transformation to SCLC after treatment with the ALK inhibitor alectinib. J Thorac Oncol. 2016;11(6):e67–72. doi: 10.1016/j.jtho.2015.12.105
  • Park S, Han J, Sun JM. Histologic transformation of ALK-rearranged adenocarcinoma to squamous cell carcinoma after treatment with ALK inhibitor. Lung Cancer. 2019;127:66–68. doi: 10.1016/j.lungcan.2018.11.027
  • Levacq D, D’Haene N, de Wind R, et al. Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: a new mechanism of resistance to ALK inhibitors. Lung Cancer. 2016;102:38–41. doi: 10.1016/j.lungcan.2016.10.012
  • Majeed U, Li S, Seegobin K, et al. First report of management of sequential small cell transformation and ALK I1171T mutation as resistance mechanisms in a patient with ALK-EML4 fused non-small cell lung adenocarcinoma with a novel combination of temozolomide and lorlatinib: a case report. JTO Clin Res Rep. 2023;4(7):100536. doi: 10.1016/j.jtocrr.2023.100536
  • Lin JJ, Shaw AT. Resisting resistance: targeted therapies in lung cancer. Trends Cancer. 2016;2(7):350–364. doi: 10.1016/j.trecan.2016.05.010
  • Ng KP, Hillmer AM, Chuah C, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med. 2021;18(4):521–528. doi: 10.1038/nm.2713
  • Marusyk A, Janiszewska M, Polyak K. Intratumor heterogeneity: the rosetta stone of therapy resistance. Cancer Cell. 2020;37(4):471–484. doi: 10.1016/j.ccell.2020.03.007
  • Dziadziuszko R, Mok T, Peters S, et al. Blood first assay screening trial (BFAST) in treatment-naive advanced or metastatic NSCLC: initial results of the phase 2 ALKPositive cohort. J Thorac Oncol. 2021;16(12):2040–2050. doi: 10.1016/j.jtho.2021.07.008
  • Sweet K, Pinilla-Ibarz J. Early switch in tyrosine kinase inhibitor therapy for patients with chronic myeloid leukemia: an emerging clinical question. Crit Rev Oncol Hematol. 2016;103:99–108. doi: 10.1016/j.critrevonc.2016.05.009
  • Soo RA, Martini JF, van der Wekken AJ, et al. Early circulating tumor DNA dynamics and efficacy of lorlatinib in patients with treatment-naive, advanced, ALK-Positive NSCLC. J Thorac Oncol. 2023;S1556-0864(23):00580–4.
  • Campo M, Al-Halabi H, Khandekar M, et al. Integration of stereotactic body radiation therapy with tyrosine kinase inhibitors in stage IV oncogene-driven lung cancer. Oncology. 2016;21(8):964–973. doi: 10.1634/theoncologist.2015-0508
  • Franceschini D, De Rose F, Cozzi S, et al. The use of radiation therapy for oligoprogressive/oligopersistent oncogene-driven non small cell lung cancer: state of the art. Crit Rev Oncol Hematol. 2020;148:102894. doi: 10.1016/j.critrevonc.2020.102894
  • Gainor JF, Chi AS, Logan J, et al. Alectinib dose escalation reinduces central nervous system responses in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer relapsing on standard dose alectinib. J Thorac Oncol. 2016;11(2):256–260. doi: 10.1016/j.jtho.2015.10.010
  • Urbanska EM, Santoni-Rugiu E, Melchior LC, et al. Intracranial response of ALK+ non-small-cell lung cancer to second-line dose-escalated brigatinib after alectinib discontinuation due to drug-induced hepatitis and relapse after whole brain radiotherapy followed by stereotactic radiosurgery. Clin Lung Cancer. 2021;22(4):e528–e532. doi: 10.1016/j.cllc.2020.04.012
  • Camidge DR, Kono SA, Lu X, et al. Anaplastic lymphoma kinase gene rearrangements in non-small cell lung cancer are associated with prolonged progression-free survival on pemetrexed.J. Thorac Oncol. 2011;6(4):774–780. doi: 10.1097/JTO.0b013e31820cf053
  • Kawamura T, Kenmotsu H, Taira T, et al. Platinum-based chemotherapy for anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer progressing on crizotinib: the differences among responders, non-responders, and patients ineligible for crizotinib. Thorac Cancer. 2018;9(2):232–240.
  • Lin J, Schoenfeld AJ, Zhu VW, et al. Efficacy of platinum/pemetrexed combination chemotherapy in ALK-Positive NSCLC refractory to second-generation ALK. Inhibitors J Thorac Oncol. 2020;15(2):258–265. doi: 10.1016/j.jtho.2019.10.014
  • Ng TL, Liu Y, Dimou A, et al. Predictive value of oncogenic driver subtype, programmed death-1 ligand (PD-L1) score, and smoking status on the efficacy of PD-1/PD-L1 inhibitors in patients with oncogene-driven non-small cell lung cancer. Cancer. 2019;125(7):1038–1049. doi: 10.1002/cncr.31871
  • Calles A, Riess JW, Brahmer JR. Checkpoint blockade in lung cancer with driver mutation: choose the road wisely. Am Soc Clin Oncol Educ Book. 2020;40(40):372–384. doi: 10.1200/EDBK_280795
  • Gainor JF, Shaw AT, Sequist LV, et al. EGFR mutations and alk rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res. 2016;22(18):4585–4593. doi: 10.1158/1078-0432.CCR-15-3101
  • Kim DW, Gadgeel S, Gettinger SN, et al. Brief report: safety and antitumor activity of alectinib plus atezolizumab from a phase 1b study in advanced ALK-Positive NSCLC. JTO Clin And Res Rep. 2022;3(8):100367. doi: 10.1016/j.jtocrr.2022.100367
  • Spigel R, Reynolds C, Waterhouse D, et al. Phase 1/2 study of the safety and tolerability of nivolumab plus crizotinib for the first-line treatment of anaplastic lymphoma kinase translocation — positive advanced non–small cell lung cancer (CheckMate 370). Journal Of Thor Oncol. 2018;13(5):682–688. doi: 10.1016/j.jtho.2018.02.022
  • Desai A, Lovly CM. Strategies to overcome resistance to ALK inhibitors in non-small cell lung cancer: a narrative review. Transl Lung Cancer Res. 2023;12(3):615–628. doi:10.21037/tlcr-22-708
  • Murray BW, Zhai D, Deng W, et al. TPX-0131, a potent CNS-penetrant, next-generation inhibitor of wild-type ALK and ALK-resistant mutations. Mol Cancer Ther. 2021;20(9):1499–1507. doi: 10.1158/1535-7163.MCT-21-0221
  • Pelish HE, Tangpeerachaikul A, Kohl NE, et al. Abstract 1468: NUV-655 (NVL-655) is a selective, brain-penetrant ALK inhibitor with antitumor activity against the lorlatinib-resistant G1202R/L1196M compound mutation. Cancer Res. 2021;81(13_Supplement):1468. doi: 10.1158/1538-7445.AM2021-1468
  • Békés M, Langley DR, Crews CM. PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov. 2022;21(3):181–200. doi: 10.1038/s41573-021-00371-6
  • Kang CH, Lee DH, Lee CO, et al. Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC). Biochem Biophys Res Commun. 2018;505(2):542–547. doi: 10.1016/j.bbrc.2018.09.169
  • Powell CE, Gao Y, Tan L, et al. Chemically induced degradation of anaplastic lymphoma kinase (ALK). J Med Chem. 2018;61(9):4249–4255. doi: 10.1021/acs.jmedchem.7b01655
  • Sun N, Ren C, Kong Y, et al. Development of a brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance. Eur J Med Chem. 2020;193:112190. doi: 10.1016/j.ejmech.2020.112190
  • Duruisseaux M, Besse B, Cadranel J, et al. Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study. Oncotarget. 2017;8(13):21903–21917. doi: 10.18632/oncotarget.15746
  • NCCN Guidelines Version 3. Non-small cell lung cancer. 2023 [cited 2023 Oct 10]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
  • Singh N, Temin S, Baker S, et al. Therapy for stage iv non–small-cell lung cancer with driver alterations: ASCO living guideline. J Clin Oncol. 2023;40(28):3310–3322. doi: 10.1200/JCO.22.00824
  • Camidge DR. Lorlatinib should not be considered as the preferred first-line option in patients with advanced ALK rearranged NSCLC. J Thoracic Oncol. 2021;16(4):528–531. doi: 10.1016/j.jtho.2020.12.022
  • Nagasaka M, S-H O. Lorlatinib should be considered as the preferred first-line option in patients with advanced ALK-Rearranged NSCLC. J Thoracic Oncol. 2021;16(4):532–536. doi: 10.1016/j.jtho.2020.12.021

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