Influence of <i>EGFR</i> co-mutation on efficacy of tyrosine kinase inhibitors in patients with non-small cell lung cancer_West China Medical Journal

Authors：

LIANG Shimeng ¹ , LI Xiaoyu ² ,  WANG Yongsheng ^1,2

1. Department of Thoracic Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

WANG Yongsheng, Email: wangys@scu.edu.cn

Keywords：

Non-small cell lung cancer; concomitant mutation; epidermal growth factor receptor; tyrosine kinase inhibitor

DOI：

10.7507/1002-0179.202111057

Video：

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Abstract Full text Figures/Tables Video References Cited by

Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.

Citation： LIANG Shimeng, LI Xiaoyu, WANG Yongsheng. Influence of EGFR co-mutation on efficacy of tyrosine kinase inhibitors in patients with non-small cell lung cancer. West China Medical Journal, 2022, 37(1): 108-115. doi: 10.7507/1002-0179.202111057 Copy

1.	Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol, 2014, 9: 154-162.
2.	Guo Y, Song J, Wang Y, et al. Concurrent genetic alterations and other biomarkers predict treatment efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer: a review. Front Oncol, 2020, 10: 610923.
3.	Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer, 2021, 21(3): 181-197.
4.	Sartori G, Belluomini L, Lombardo F, et al. Efficacy and safety of afatinib for non-small-cell lung cancer: state-of-the-art and future perspectives. Expert Rev Anticancer Ther, 2020, 20(7): 531-542.
5.	Passaro A, Mok T, Peters S, et al. Recent advances on the role of EGFR tyrosine kinase inhibitors in the management of NSCLC with uncommon, non exon 20 insertions, EGFR mutations. J Thorac Oncol, 2021, 16(5): 764-773.
6.	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.
7.	Keam B, Kim DW, Park JH, et al. Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer. Int J Clin Oncol, 2014, 19(4): 594-600.
8.	Xu J, Jin B, Chu T, et al. EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: a real-world study in China. Lung Cancer, 2016, 96(96): 87-92.
9.	Wu JY, Shih JY. Effectiveness of tyrosine kinase inhibitors on uncommon E709X epidermal growth factor receptor mutations in non-small-cell lung cancer. Onco Targets Ther, 2016, 9(9): 6137-6145.
10.	Baek JH, Sun JM, Min YJ, et al. Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer except both exon 19 deletion and exon 21 L858R: a retrospective analysis in Korea. Lung Cancer, 2015(87): 148-154.
11.	Chiu CH, Yang CT, Shih JY, 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.
12.	Hayashi T, Kohsaka S, Takamochi K, et al. Clinicopathological characteristics of lung adenocarcinoma with compound EGFR mutations. Hum Pathol, 2020, 103(103): 42-51.
13.	Yang JC, Schuler M, Popat S, et al. Afatinib for the treatment of NSCLC harboring uncommon EGFR mutations: a database of 693 cases. J Thorac Oncol, 2020, 15(5): 803-815.
14.	Tan J, Hu C, Deng P, et al. The predictive values of advanced non-small cell lung cancer patients harboring uncommon EGFR mutations-the mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations. Front Oncol, 2021, 11: 646577.
15.	Cai Y, Wang Y, Sun J, et al. Successful treatment of a patient with NSCLC carrying uncommon compound EGFR G719X and S768I mutations using osimertinib: a case report. J Int Med Res, 2020, 48: 300060520928793.
16.	Yang M, Tong X, Xu X, et al. Case report: osimertinib achieved remarkable and sustained disease control in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M mutation complex. Lung Cancer, 2018(121): 1-4.
17.	Levine AJ. Spontaneous and inherited TP53 genetic alterations. Oncogene, 2021, 40: 5975-5983.
18.	Neumann MP, Gonzalez MV, Pitiot AS, et al. TP53 p. R72P genotype is a marker of poor prognosis in lung cancer. Cancer Biomark, 2018, 21: 747-754.
19.	Jiao XD, Qin BD, You P, et al. The prognostic value of TP53 and its correlation with EGFR mutation in advanced non-small cell lung cancer, an analysis based on cBioPortal data base. Lung Cancer, 2018, 123(123): 70-75.
20.	张乾坤, 郝吉庆. TP53/EGFR 基因共突变对肺腺癌患者 EGFR-TKIs 疗效的影响. 安徽医科大学学报, 2019, 54(6): 967-971.
21.	Iwama E, Sakai K, Azuma K, et al. Exploration of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next-generation sequencing. Cancer Sci, 2018, 109(12): 3921-3933.
22.	Yang X, Xia Y, Xu L, et al. Efficacy and safety of combination treatment with apatinib and osimertinib after osimertinib resistance in epidermal growth factor receptor-mutant non-small cell lung carcinoma: a retrospective analysis of a multicenter clinical study. Front Mol Biosci, 2021, 8: 639892.
23.	Rachiglio AM, Fenizia F, Piccirillo MC, et al. The presence of concomitant mutations affects the activity of EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer (NSCLC) patients. Cancers (Basel), 2019, 11(3): 341.
24.	Cheng Y, Ma L, Liu Y, et al. Comprehensive characterization and clinical impact of concomitant genomic alterations in EGFR-mutant NSCLCs treated with EGFR kinase inhibitors. Lung Cancer, 2020, 145: 63-70.
25.	Poeta ML, Manola J, Goldwasser MA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med, 2007, 357(25): 2552-2561.
26.	Molina-Vila M, Bertran-Alamillo J, Gascó A, et al. Nondisruptive p53 mutations are associated with shorter survival in patients with advanced non-small cell lung cancer. Clin Cancer Res, 2014, 20(17): 4647-4659.
27.	Labbe C, Cabanero M, Korpanty GJ, et al. Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Lung Cancer, 2017, 111: 23-29.
28.	Willis O, Choucair K, Alloghbi A, et al. PIK3CA gene aberrancy and role in targeted therapy of solid malignancies. Cancer Gene Ther, 2020, 27(9): 634-644.
29.	Guo Y, Cao R, Zhang X, et al. Recent progress in rare oncogenic drivers and targeted therapy for non-small cell lung cancer. Onco Targets Ther, 2019, 12(12): 10343-10360.
30.	Zhao J, Han Y, Li J, et al. Prognostic value of KRAS/TP53/PIK3CA in non-small cell lung cancer. Oncol Lett, 2019, 17(3): 3233-3240.
31.	Wang Y, Wang Y, Li J, et al. Clinical significance of PIK3CA gene in non-small-cell lung cancer: a systematic review and meta-analysis. Biomed Res Int, 2020, 2020: 3608241.
32.	Eng J, Woo KM, Sima CS, et al. Impact of concurrent PIK3CA mutations on response to EGFR tyrosine kinase inhibition in EGFR-mutant lung cancers and on prognosis in oncogene-driven lung adenocarcinomas. J Thorac Oncol, 2015, 10(12): 1713-1719.
33.	Qiu X, Wang Y, Liu F, et al. Survival and prognosis analyses of concurrent PIK3CA mutations in EGFR mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors. Am J Cancer Res, 2021, 11(6): 3189-3200.
34.	李向敏, 樊再雯, 张兰兰. 原发 EGFR(19 del)和 PIK3CA(Exon 2)共突变非小细胞肺癌 1 例报道并文献复习. 肿瘤防治研究, 2020, 47(5): 398-400.
35.	Martín MP, Huerta M, Compañ QA, et al. Coexistence of EGFR, KRAS, BRAF, and PIK3CA mutations and ALK rearrangement in a comprehensive cohort of 326 consecutive Spanish nonsquamous NSCLC patients. Clin Lung Cancer, 2017, 18(6): e395-e402.
36.	Wu SG, Chang YL, Yu CJ, et al. The role of PIK3CA mutations among lung adenocarcinoma patients with primary and acquired resistance to EGFR tyrosine kinase inhibition. Sci Rep, 2016, 6: 35249.
37.	Rosas G, Ruiz R, Araujo JM, et al. ALK rearrangements: biology, detection and opportunities of therapy in non-small cell lung cancer. Crit Rev Oncol Hematol, 2019, 136(136): 48-55.
38.	Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1, 683 patients with non-small cell lung cancer. Clin Cancer Res, 2013, 19(15): 4273-4281.
39.	Fan J, Dai X, Wang Z, et al. Concomitant EGFR mutation and EML4-ALK rearrangement in lung adenocarcinoma is more frequent in multifocal lesions. Clin Lung Cancer, 2019, 20(4): e517-e530.
40.	Popat S, Vieira DA, Min T, et al. Lung adenocarcinoma with concurrent exon 19 EGFR mutation and ALK rearrangement responding to erlotinib. J Thorac Oncol, 2011(6): 1962-1963.
41.	Yang JJ, Zhang XC, Su J, et al. Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation. Clin Cancer Res, 2014, 20(5): 1383-1392.
42.	Lou NN, Zhang XC, Chen HJ, et al. Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutation, ALK rearrangement and EGFR/ALK co-alterations. Oncotarget, 2016, 7(40): 65185-65195.
43.	Tiseo M, Gelsomino F, Boggiani D, et al. EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant patient with both concomitant mutations. Lung Cancer, 2011, 71(2): 241-243.
44.	Won JK, Keam B, Koh J, et al. Concomitant ALK translocation and EGFR mutation in lung cancer: a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor. Ann Oncol, 2015, 26(2): 348-354.
45.	Sahnane N, Frattini M, Bernasconi B, et al. EGFR and KRAS mutations in ALK-positive lung adenocarcinomas: biological and clinical effect. Clin Lung Cancer, 2016, 17(1): 56-61.
46.	Sweis RF, Thomas S, Bank B, et al. Concurrent EGFR mutation and ALK Translocation in non-small cell lung cancer. Cureus, 2016, 8: e513.
47.	Kuo YW, Wu SG, Ho CC, et al. Good response to gefitinib in lung adenocarcinoma harboring coexisting EML4-ALK fusion gene and EGFR mutation. J Thorac Oncol, 2010, 5(12): 2039-2040.
48.	Drilon A, Jenkins C, Iyer S, et al. ROS1-dependent cancers: biology, diagnostics and therapeutics. Nat Rev Clin Oncol, 2021, 18(1): 35-55.
49.	Remon J, Pignataro D, Novello S, et al. Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer. Cancer Treat Rev, 2021, 95: 102178.
50.	Zhang Y, Wang H, Wang X, et al. Precision treatment of advanced lung adenocarcinoma with coexisting EGFR, ALK, and ROS1 mutations: a case report. Clin Lung Cancer, 2021, 22(5): e699-e702.
51.	Ju L, Han M, Zhao C, et al. KRAS and ROS1 variants coexist in a lung adenocarcinoma patient. Lung Cancer, 2016(95): 94-97.
52.	Wiesweg M, Eberhardt W, Reis H, et al. High prevalence of concomitant oncogene mutations in prospectively identified patients with ROS1-positive metastatic lung cancer. J Thorac Oncol, 2017, 12(1): 54-64.
53.	Lambros L, Guibourg B, Uguen A. ROS1-rearranged non-small cell lung cancers with concomitant oncogenic driver alterations: about some rare therapeutic dilemmas. Clin Lung Cancer, 2018, 19(1): e73-e74.
54.	Mao Y, Wu S. ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma. Onco Targets Ther, 2017, 10: 3399-3404.

1. Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol, 2014, 9: 154-162.
2. Guo Y, Song J, Wang Y, et al. Concurrent genetic alterations and other biomarkers predict treatment efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer: a review. Front Oncol, 2020, 10: 610923.
3. Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer, 2021, 21(3): 181-197.
4. Sartori G, Belluomini L, Lombardo F, et al. Efficacy and safety of afatinib for non-small-cell lung cancer: state-of-the-art and future perspectives. Expert Rev Anticancer Ther, 2020, 20(7): 531-542.
5. Passaro A, Mok T, Peters S, et al. Recent advances on the role of EGFR tyrosine kinase inhibitors in the management of NSCLC with uncommon, non exon 20 insertions, EGFR mutations. J Thorac Oncol, 2021, 16(5): 764-773.
6. 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.
7. Keam B, Kim DW, Park JH, et al. Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer. Int J Clin Oncol, 2014, 19(4): 594-600.
8. Xu J, Jin B, Chu T, et al. EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: a real-world study in China. Lung Cancer, 2016, 96(96): 87-92.
9. Wu JY, Shih JY. Effectiveness of tyrosine kinase inhibitors on uncommon E709X epidermal growth factor receptor mutations in non-small-cell lung cancer. Onco Targets Ther, 2016, 9(9): 6137-6145.
10. Baek JH, Sun JM, Min YJ, et al. Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer except both exon 19 deletion and exon 21 L858R: a retrospective analysis in Korea. Lung Cancer, 2015(87): 148-154.
11. Chiu CH, Yang CT, Shih JY, 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.
12. Hayashi T, Kohsaka S, Takamochi K, et al. Clinicopathological characteristics of lung adenocarcinoma with compound EGFR mutations. Hum Pathol, 2020, 103(103): 42-51.
13. Yang JC, Schuler M, Popat S, et al. Afatinib for the treatment of NSCLC harboring uncommon EGFR mutations: a database of 693 cases. J Thorac Oncol, 2020, 15(5): 803-815.
14. Tan J, Hu C, Deng P, et al. The predictive values of advanced non-small cell lung cancer patients harboring uncommon EGFR mutations-the mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations. Front Oncol, 2021, 11: 646577.
15. Cai Y, Wang Y, Sun J, et al. Successful treatment of a patient with NSCLC carrying uncommon compound EGFR G719X and S768I mutations using osimertinib: a case report. J Int Med Res, 2020, 48: 300060520928793.
16. Yang M, Tong X, Xu X, et al. Case report: osimertinib achieved remarkable and sustained disease control in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M mutation complex. Lung Cancer, 2018(121): 1-4.
17. Levine AJ. Spontaneous and inherited TP53 genetic alterations. Oncogene, 2021, 40: 5975-5983.
18. Neumann MP, Gonzalez MV, Pitiot AS, et al. TP53 p. R72P genotype is a marker of poor prognosis in lung cancer. Cancer Biomark, 2018, 21: 747-754.
19. Jiao XD, Qin BD, You P, et al. The prognostic value of TP53 and its correlation with EGFR mutation in advanced non-small cell lung cancer, an analysis based on cBioPortal data base. Lung Cancer, 2018, 123(123): 70-75.
20. 张乾坤, 郝吉庆. TP53/EGFR 基因共突变对肺腺癌患者 EGFR-TKIs 疗效的影响. 安徽医科大学学报, 2019, 54(6): 967-971.
21. Iwama E, Sakai K, Azuma K, et al. Exploration of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next-generation sequencing. Cancer Sci, 2018, 109(12): 3921-3933.
22. Yang X, Xia Y, Xu L, et al. Efficacy and safety of combination treatment with apatinib and osimertinib after osimertinib resistance in epidermal growth factor receptor-mutant non-small cell lung carcinoma: a retrospective analysis of a multicenter clinical study. Front Mol Biosci, 2021, 8: 639892.
23. Rachiglio AM, Fenizia F, Piccirillo MC, et al. The presence of concomitant mutations affects the activity of EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer (NSCLC) patients. Cancers (Basel), 2019, 11(3): 341.
24. Cheng Y, Ma L, Liu Y, et al. Comprehensive characterization and clinical impact of concomitant genomic alterations in EGFR-mutant NSCLCs treated with EGFR kinase inhibitors. Lung Cancer, 2020, 145: 63-70.
25. Poeta ML, Manola J, Goldwasser MA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med, 2007, 357(25): 2552-2561.
26. Molina-Vila M, Bertran-Alamillo J, Gascó A, et al. Nondisruptive p53 mutations are associated with shorter survival in patients with advanced non-small cell lung cancer. Clin Cancer Res, 2014, 20(17): 4647-4659.
27. Labbe C, Cabanero M, Korpanty GJ, et al. Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Lung Cancer, 2017, 111: 23-29.
28. Willis O, Choucair K, Alloghbi A, et al. PIK3CA gene aberrancy and role in targeted therapy of solid malignancies. Cancer Gene Ther, 2020, 27(9): 634-644.
29. Guo Y, Cao R, Zhang X, et al. Recent progress in rare oncogenic drivers and targeted therapy for non-small cell lung cancer. Onco Targets Ther, 2019, 12(12): 10343-10360.
30. Zhao J, Han Y, Li J, et al. Prognostic value of KRAS/TP53/PIK3CA in non-small cell lung cancer. Oncol Lett, 2019, 17(3): 3233-3240.
31. Wang Y, Wang Y, Li J, et al. Clinical significance of PIK3CA gene in non-small-cell lung cancer: a systematic review and meta-analysis. Biomed Res Int, 2020, 2020: 3608241.
32. Eng J, Woo KM, Sima CS, et al. Impact of concurrent PIK3CA mutations on response to EGFR tyrosine kinase inhibition in EGFR-mutant lung cancers and on prognosis in oncogene-driven lung adenocarcinomas. J Thorac Oncol, 2015, 10(12): 1713-1719.
33. Qiu X, Wang Y, Liu F, et al. Survival and prognosis analyses of concurrent PIK3CA mutations in EGFR mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors. Am J Cancer Res, 2021, 11(6): 3189-3200.
34. 李向敏, 樊再雯, 张兰兰. 原发 EGFR(19 del)和 PIK3CA(Exon 2)共突变非小细胞肺癌 1 例报道并文献复习. 肿瘤防治研究, 2020, 47(5): 398-400.
35. Martín MP, Huerta M, Compañ QA, et al. Coexistence of EGFR, KRAS, BRAF, and PIK3CA mutations and ALK rearrangement in a comprehensive cohort of 326 consecutive Spanish nonsquamous NSCLC patients. Clin Lung Cancer, 2017, 18(6): e395-e402.
36. Wu SG, Chang YL, Yu CJ, et al. The role of PIK3CA mutations among lung adenocarcinoma patients with primary and acquired resistance to EGFR tyrosine kinase inhibition. Sci Rep, 2016, 6: 35249.
37. Rosas G, Ruiz R, Araujo JM, et al. ALK rearrangements: biology, detection and opportunities of therapy in non-small cell lung cancer. Crit Rev Oncol Hematol, 2019, 136(136): 48-55.
38. Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1, 683 patients with non-small cell lung cancer. Clin Cancer Res, 2013, 19(15): 4273-4281.
39. Fan J, Dai X, Wang Z, et al. Concomitant EGFR mutation and EML4-ALK rearrangement in lung adenocarcinoma is more frequent in multifocal lesions. Clin Lung Cancer, 2019, 20(4): e517-e530.
40. Popat S, Vieira DA, Min T, et al. Lung adenocarcinoma with concurrent exon 19 EGFR mutation and ALK rearrangement responding to erlotinib. J Thorac Oncol, 2011(6): 1962-1963.
41. Yang JJ, Zhang XC, Su J, et al. Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation. Clin Cancer Res, 2014, 20(5): 1383-1392.
42. Lou NN, Zhang XC, Chen HJ, et al. Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutation, ALK rearrangement and EGFR/ALK co-alterations. Oncotarget, 2016, 7(40): 65185-65195.
43. Tiseo M, Gelsomino F, Boggiani D, et al. EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant patient with both concomitant mutations. Lung Cancer, 2011, 71(2): 241-243.
44. Won JK, Keam B, Koh J, et al. Concomitant ALK translocation and EGFR mutation in lung cancer: a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor. Ann Oncol, 2015, 26(2): 348-354.
45. Sahnane N, Frattini M, Bernasconi B, et al. EGFR and KRAS mutations in ALK-positive lung adenocarcinomas: biological and clinical effect. Clin Lung Cancer, 2016, 17(1): 56-61.
46. Sweis RF, Thomas S, Bank B, et al. Concurrent EGFR mutation and ALK Translocation in non-small cell lung cancer. Cureus, 2016, 8: e513.
47. Kuo YW, Wu SG, Ho CC, et al. Good response to gefitinib in lung adenocarcinoma harboring coexisting EML4-ALK fusion gene and EGFR mutation. J Thorac Oncol, 2010, 5(12): 2039-2040.
48. Drilon A, Jenkins C, Iyer S, et al. ROS1-dependent cancers: biology, diagnostics and therapeutics. Nat Rev Clin Oncol, 2021, 18(1): 35-55.
49. Remon J, Pignataro D, Novello S, et al. Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer. Cancer Treat Rev, 2021, 95: 102178.
50. Zhang Y, Wang H, Wang X, et al. Precision treatment of advanced lung adenocarcinoma with coexisting EGFR, ALK, and ROS1 mutations: a case report. Clin Lung Cancer, 2021, 22(5): e699-e702.
51. Ju L, Han M, Zhao C, et al. KRAS and ROS1 variants coexist in a lung adenocarcinoma patient. Lung Cancer, 2016(95): 94-97.
52. Wiesweg M, Eberhardt W, Reis H, et al. High prevalence of concomitant oncogene mutations in prospectively identified patients with ROS1-positive metastatic lung cancer. J Thorac Oncol, 2017, 12(1): 54-64.
53. Lambros L, Guibourg B, Uguen A. ROS1-rearranged non-small cell lung cancers with concomitant oncogenic driver alterations: about some rare therapeutic dilemmas. Clin Lung Cancer, 2018, 19(1): e73-e74.
54. Mao Y, Wu S. ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma. Onco Targets Ther, 2017, 10: 3399-3404.

West China Medical Journal

Influence of EGFR co-mutation on efficacy of tyrosine kinase inhibitors in patients with non-small cell lung cancer

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