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Review Articles

Four generations of EGFR TKIs associated with different pathogenic mutations in non-small cell lung carcinoma

, , & ORCID Icon
Pages 861-872 | Received 28 Sep 2019, Accepted 29 Feb 2020, Published online: 12 Mar 2020

References

  • Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. N Engl J Med. 2002;346(2):92–98.
  • Bonomi P, Kim KM, Fairclough D, et al. Comparison of survival and quality of life in advanced non–small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an eastern cooperative oncology group trial. J Clin Oncol. 2000;18(3):623–631.
  • Moasser MM. Targeting the function of the HER2 oncogene in human cancer therapeutics. Oncogene. 2007;26(46):6577–6592.
  • Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366(1):2–16.
  • Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008;358(11):1160–1174.
  • Manegold C, Dingemans A-M, Gray JE, et al. The potential of combined immunotherapy and antiangiogenesis for the synergistic treatment of advanced NSCLC. J Thorac Oncol. 2017;12(2):194–207.
  • Camidge DR, Doebele RC, Kerr KM. Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC. Nat Rev Clin Oncol. 2019;16(6):341–355.
  • Russo A, Franchina T, Ricciardi GRR, et al. The changing scenario of 1 line therapy in non-oncogene addicted NSCLCs in the era of immunotherapy. Crit Rev Oncol Hematol. 2018;130:1–12.
  • Remon J, Ahn M-J, Girard N, et al. Advanced-stage non-small cell lung cancer: advances in thoracic oncology 2018. J Thorac Oncol. 2019;14(7):1134–1155.
  • Gettinger S, Rizvi NA, Chow LQ, et al. Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2016;34(25):2980–2987.
  • Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–2028.
  • Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092.
  • Kobayashi S, Canepa HM, Bailey AS, et al. Compound EGFR mutations and response to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8(1):118–151.
  • Cadranel J, Zalcman G, Sequist L. Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer. Eur Respir J. 2011;37(1):183–193.
  • Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169–181.
  • Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008;359(4):366–377.
  • Rosell R, Molina MA, Costa C, et al. Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clin Cancer Res. 2011;17(5):1160–1168.
  • Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. Plos Med. 2005;2(3):e73.
  • Balak MN, Gong Y, Riely GJ, et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 2006;12(21):6494–6501.
  • Wu JY, Jin-Yuan S. Effectiveness of tyrosine kinase inhibitors on uncommon E709X epidermal growth factor receptor mutations in non-small-cell lung cancer. Onco Targets Ther. 2016;9:6137–6145.
  • Yang TY, Tsai C-R, Chen K-C, et al. Good response to gefitinib in a lung adenocarcinoma harboring a heterozygous complex mutation of L833V and H835L in epidermal growth factor receptor gene. J Clin Oncol. 2011;29(16):e468–e469.
  • Qin BD, Xiao-Dong J, Ling-Yan Y, et al. The effectiveness of afatinib and osimertinib in a Chinese patient with advanced lung adenocarcinoma harboring a rare triple EGFR mutation (R670W/H835L/L833V): a case report and literature review. Onco Targets Ther. 2018;11:4739–4745.
  • Kobayashi Y, Mitsudomi T. Not all epidermal growth factor receptor mutations in lung cancer are created equal: perspectives for individualized treatment strategy. Cancer Sci. 2016;107(9):1179–1186.
  • Chiu C-H, Yang C-T, Shih J-Y, et al. Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. J Thorac Oncol. 2015;10(5):793–799.
  • Zhang X, Chang A. Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer. J Med Genet. 2006;44(3):166–172.
  • Masago K, Miura M, Toyama Y, et al. Good clinical response to erlotinib in a patient with anaplastic thyroid carcinoma harboring an epidermal growth factor somatic mutation, L858R, in exon 21. J Clin Oncol. 2011;29(16):e465–7.
  • Ercan D, Choi HG, Yun C-H, et al. EGFR mutations and resistance to irreversible pyrimidine-based EGFR inhibitors. Clin Cancer Res. 2015;21(17):3913–3923.
  • Bersanelli M, Minari R, Bordi P, et al. L718Q mutation as new mechanism of acquired resistance to AZD9291 in EGFR-mutated NSCLC. J Thorac Oncol. 2016;11(10):e121–e123.
  • Ou S-H, Cui J, Schrock AB, et al. Emergence of novel and dominant acquired EGFR solvent-front mutations at Gly796 (G796S/R) together with C797S/R and L792F/H mutations in one EGFR (L858R/T790M) NSCLC patient who progressed on osimertinib. Lung Cancer. 2017;108:228–231.
  • Chen K, Zhou F, Shen W, et al. Novel mutations on EGFR Leu792 potentially correlate to acquired resistance to osimertinib in advanced NSCLC. J Thorac Oncol. 2017;12(6):e65–e68.
  • Zhang Q, Zhang X-C, Yang J-J, et al. EGFR L792H and G796R: two novel mutations mediating resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib. J Thorac Oncol. 2018;13(9):1415–1421.
  • Zheng D, Hu M, Bai Y, et al. EGFR G796D mutation mediates resistance to osimertinib. Oncotarget. 2017;8(30):49671.
  • Chabon JJ, Simmons AD, Lovejoy AF, et al. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016;7(1):11815.
  • Bean J, Riely GJ, Balak M, et al. Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res. 2008;14(22):7519–7525.
  • Gainor JF, Shaw AT. Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. J Clin Oncol. 2013;31(31):3987–3996.
  • Costa DB, Halmos B, Kumar A, et al. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med. 2007;4(10):e315.
  • Costa DB, Schumer ST, Tenen DG, et al. Differential responses to erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations. J Clin Oncol. 2008;26(7):1182–1184.
  • Chiba M, Togashi Y, Bannno E, et al. Efficacy of irreversible EGFR TKIs for the uncommon secondary resistant EGFR mutations L747S, D761Y, and T854A. BMC Cancer. 2017;17(1):281.
  • Frega S, Conte P, Fassan M, et al. A triple rare E709K and L833V/H835L EGFR mutation responsive to an irreversible Pan-HER inhibitor: a case report of lung adenocarcinoma treated with afatinib. J Thorac Oncol. 2016;11(5):e63–e64.
  • Lee Y, Kim TM, Kim DW, et al. Preclinical modeling of osimertinib for NSCLC with EGFR Exon 20 insertion mutations. J Thorac Oncol. 2019;14(9):1556–1566.
  • Yang Z, Yang N, Ou Q, et al. Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients. Clin Cancer Res. 2018;24(13):3097–3107.
  • Masuzawa K, Yasuda H, Hamamoto J, et al. Characterization of the efficacies of osimertinib and nazartinib against cells expressing clinically relevant epidermal growth factor receptor mutations. Oncotarget. 2017;8(62):105479.
  • Han J-Y, Park K, Kim S-W, et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol. 2012;30(10):1122–1128.
  • Zhou Q, Yang J-J, Chen Z-H, et al. Serial cfDNA assessment of response and resistance to EGFR TKI for patients with EGFR-L858R mutant lung cancer from a prospective clinical trial. J Hematol Oncol. 2016;9(1):86.
  • Shi Y, Zhang L, Liu X, et al. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013;14(10):953–961.
  • Katakami N, Morita S, Yoshioka H, et al. Randomized phase III study comparing gefitinib (G) with erlotinib (E) in patients (pts) with previously treated advanced lung adenocarcinoma (LA): WJOG 5108L. J Clin Oncol. 2014;34:3248–3257.
  • Yun C-H, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci. 2008;105(6):2070–2075.
  • Planchard D, Loriot Y, André F, et al. EGFR independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients. Ann Oncol. 26(10):2073–2078.
  • Jia Y, Juarez J, Li J, et al. EGF816 exerts anticancer effects in non-small cell lung cancer by irreversibly and selectively targeting primary and acquired activating mutations in the EGF receptor. Cancer Res. 2016;76(6):1591–1602.
  • Helena AY, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 2013;19(8):2240–2247.
  • Kosaka T, Yatabe Y, Endoh H, et al. Analysis of epidermal growth factor receptor gene mutation in patients with non–small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res. 2006;12(19):5764–5769.
  • Del Re M, Tiseo M, Bordi P, et al. Contribution of KRAS mutations and c. 2369C > T (p. T790M) EGFR to acquired resistance to EGFR TKIs in EGFR mutant NSCLC: a study on circulating tumor DNA. Oncotarget. 2017;8(8):13611.
  • Sos ML, Koker M, Weir BA, et al. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res. 2009;69(8):3256–3261.
  • Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27(34):4702–4711.
  • Park K, Tan E-H, O'Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016;17(5):577–589.
  • Wu Y-L, Zhou C, Hu C-P, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213–222.
  • Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther. 2012;343(2):342–350.
  • Yap TA, Vidal L, Adam J, et al. Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol. 2010;28(25):3965–3972.
  • Janjigian YY, Smit EF, Groen HJ, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor–resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014;4(9):1036–1045.
  • Cho BC, Kim H-J, Lim SM. Enhancement of the anti-tumor activity of afatinib by inhibition of glycolysis in non-small cell lung cancer harboring the EGFR T790M mutation. AACR Cancer Res. 2013;73(Supp 8):5408–5408.
  • Lee Y, Wang Y, James M, et al. Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells. Mol Carcinog. 2016;55(5):991–1001.
  • Wu S-G, Liu Y-N, Tsai M-F, et al. The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients. Oncotarget. 2016;7(11):12404.
  • Cross DAE, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discove. 2014;4(9):1046–1061.
  • Meador CB, Jin H, de Stanchina E, et al. Optimizing the sequence of anti-EGFR-targeted therapy in EGFR-mutant lung cancer. Mol Cancer Ther. 2015;14(2):542–552.
  • Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall survival with osimertinib in untreated, -mutated advanced NSCLC. N Engl J Med. 2019;382(1):41–50.
  • Proto C, Imbimbo M, Gallucci R, et al. Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: the present and the future. Transl Lung Cancer Res. 2016;5(6):563–578.
  • Hochmair M. Medical treatment options for patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer suffering from brain metastases and/or leptomeningeal disease. Targ Oncol. 2018;13(3):269–285.
  • de Vries NA, Buckle T, Zhao J, et al. Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs. 2012;30(2):443–449.
  • Ballard P, Yates JWT, Yang Z, et al. Preclinical comparison of osimertinib with other EGFR TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130–5140.
  • Hong MH, Lee IY, Koh JS, et al. P3.02b-119 YH25448, a highly selective 3rd generation EGFR TKI, exhibits superior survival over osimertinib in animal model with brain metastases from NSCLC: topic: EGFR RES. J Thorac Oncol. 2017;12(1):S1265–S1266.
  • Ahn M-J, Han J-Y, Lee KH, et al. Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1-2 study. Lancet Oncol. 2019;20(12):1681–1690.
  • Yun J, Hong MH, Kim S-Y, et al. YH25448, an irreversible EGFR TKI with potent intracranial activity in EGFR mutant non-small cell lung cancer. Clin Cancer Res. 2019;25(8):2575–2587.
  • Tan D-W, Yang J-H, Leighl NB, et al. Updated results of a phase 1 study of EGF816, a third-generation, mutant-selective EGFR tyrosine kinase inhibitor (TKI), in advanced non-small cell lung cancer (NSCLC) harboring T790M. Am Soc Clin Oncol. 2016;34(Supp):9044.
  • Xu X, Mao L, Xu W, et al. AC0010, an irreversible EGFR inhibitor selectively targeting mutated EGFR and overcoming T790M-induced resistance in animal models and lung cancer patients. Mol Cancer Ther. 2016;15(11):2586–2597.
  • Ma Y, Zheng X, Zhao H, et al. First-in-human phase I study of AC0010, a mutant-selective EGFR inhibitor in non-small cell lung cancer: safety, efficacy, and potential mechanism of resistance. J Thorac Oncol. 2018;13(7):968–977.
  • Van Der Steen N, Caparello C, Rolfo C, et al. New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong? Onco Targets Ther. 2016;9:6065–6074.
  • Murtuza A, Bulbul A, Shen JP, et al. Novel third-generation EGFR tyrosine kinase inhibitors and strategies to overcome therapeutic resistance in lung cancer. Cancer Res. 2019;79(4):689–698.
  • Kelly RJ, Shepherd FA, Krivoshik A, et al. A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer. Ann Oncol. 2019;30(7):1127–1133.
  • Yu HA, Spira A, Horn L, et al. A phase I, dose escalation study of oral ASP8273 in patients with non-small cell lung cancers with epidermal growth factor receptor mutations. Clin Cancer Res. 2017;23(24):7467–7473.
  • Hutchinson L. Lung cancer: AURA3 magic reveals new standard. Nat Rev Clin Oncol. 2017;14(2):69–69.
  • Wu Y-L, Ahn M-J, Garassino MC, et al. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018;36(26):2702–2709.
  • Reungwetwattana T, Nakagawa K, Cho BC, et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018;JCO2018783118.
  • Thress KS, Paweletz CP, Felip E, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non–small cell lung cancer harboring EGFR T790M. Nat Med. 2015;21(6):560–562.
  • Jia Y, Yun C-H, Park E, et al. Overcoming EGFR (T790M) and EGFR (C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016;534(7605):129–132.
  • Niederst MJ, Hu H, Mulvey HE, et al. The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies. Clin Cancer Res. 2015;21(17):3924–3933.
  • Wang Z, Yang J-J, Huang J, et al. Lung adenocarcinoma harboring EGFR T790M and in trans C797S responds to combination therapy of first-and third-generation EGFR TKIs and shifts allelic configuration at resistance. J Thorac Oncol. 2017;12(11):1723–1727.
  • Uchibori K, Inase N, Araki M, et al. Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nat Commun. 2017;8(1):14768.
  • Kim TM, Song A, Kim D-W, et al. Mechanisms of acquired resistance to AZD9291: a mutation-selective, irreversible EGFR inhibitor. J Thorac Oncol. 2015;10(12):1736–1744.
  • Ho C-C, Liao W-Y, Lin C-A, et al. Acquired BRAF V600E mutation as resistant mechanism after treatment with osimertinib. J Thorac Oncol. 2017;12(3):567–572.
  • Ortiz-Cuaran S, Scheffler M, Plenker D, et al. Heterogeneous mechanisms of primary and acquired resistance to third-generation EGFR inhibitors. Clin Cancer Res. 2016;22(19):4837–4847.
  • Ramalingam SS, Yang JCH, Lee CK, et al. Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J Clin Oncol. 2018;36(9):841–849.
  • Ramalingam S, Cheng Y, Zhou C, et al. LBA50Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. Ann Oncol. 2018;29:viii740.
  • Costa DB, Kobayashi SS. Whacking a mole-cule: clinical activity and mechanisms of resistance to third generation EGFR inhibitors in EGFR mutated lung cancers with EGFR-T790M. Transl Lung Cancer Res. 2015;4(6):809–815.
  • Uchibori K, Inase N, Nishio M, et al. Identification of mutation accumulation as resistance mechanism emerging in first-line osimertinib treatment. J Thorac Oncol. 2018;13(7):915–925.
  • Fassunke J, Müller F, Keul M, et al. Overcoming EGFR(G724S)-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors. Nat Commun. 2018;9(1):4655–4655.
  • Michels S, Heydt C, Veggel B, et al. Genomic profiling identifies outcome-relevant mechanisms of innate and acquired resistance to third-generation epidermal growth factor receptor tyrosine kinase inhibitor therapy in lung cancer. JCO Precis Oncol. 2019;2019:(3):1–14.
  • Oxnard GR, Hu Y, Mileham KF, et al. Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib. JAMA Oncol. 2018;4(11):1527–1534.
  • Piotrowska Z, Hazar-Rethinam M, Rizzo C, et al. Heterogeneity and coexistence of T790M and T790 wild-type resistant subclones drive mixed response to third-generation epidermal growth factor receptor inhibitors in lung cancer. JCO Precis Oncol. 2018;2018(2):1–15.
  • Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014;15(11):1236–1244.
  • Rosell R, Dafni U, Felip E, et al. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 2017;5(5):435–444.
  • Saito H, Fukuhara T, Furuya N, et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019;20(5):625–635.
  • Stinchcombe TE, Jänne PA, Wang X, et al. Effect of erlotinib plus bevacizumab vs erlotinib alone on progression-free survival in patients with advanced EGFR-mutant non-small cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2019;5(10):1448.
  • Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655–1669.
  • Shah KN, Bhatt R, Rotow J, et al. Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer. Nat Med. 2019;25(1):111–118.
  • Sequist LV, Lee JS, Han J-Y, et al. Abstract CT033: TATTON Phase Ib expansion cohort: Osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Cancer Res. 2019;79(13):CT033.
  • Noronha V, Patil VM, Joshi A, et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in -mutated lung cancer. J Clin Oncol. 2019;38(2):124–136.
  • Guo X-F, Zhu X-F, Shang Y, et al. A bispecific enediyne-energized fusion protein containing ligand-based and antibody-based oligopeptides against epidermal growth factor receptor and human epidermal growth factor receptor 2 shows potent antitumor activity. Clin Cancer Res. 2010;16(7):2085–2094.
  • Guo X-F, Zhu X-F, Yang W-C, et al. An EGFR/HER2-Bispecific and enediyne-energized fusion protein shows high efficacy against esophageal cancer. PLoS One. 2014;9(3):e92986.
  • Cao R, Song W, Ye C, et al. Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer. Cancer Med. 2019;8(2):643–655.
  • Xu J, Du Y, Liu X-J, et al. Recombinant EGFR/MMP-2 bi-targeted fusion protein markedly binding to non-small-cell lung carcinoma and exerting potent therapeutic efficacy. Pharmacol Res. 2017;126:66–76.
  • Mondal G, Almawash S, Chaudhary AK, et al. EGFR-targeted cationic polymeric mixed micelles for codelivery of gemcitabine and miR-205 for treating advanced pancreatic cancer. Mol Pharmaceutics. 2017;14(9):3121–3133.
  • Li Z, Wang M, Yao X, et al. Development of a Novel EGFR-targeting antibody-drug conjugate for pancreatic cancer therapy. Target Oncol. 2019;14(1):93–105.

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