Molecular targeted therapy for non-small cell lung cancer has significantly improved clinical outcomes in patients with driver gene-positive tumors. Nevertheless, treatment-related adverse drug reactions (ADRs) present challenges to patients' quality of life and treatment adherence. Given the broad clinical utilization of various targeted agents, it is imperative to comprehensively characterize and standardize the management of these ADRs. This review systematically synthesizes the common and unique spectra of ADRs associated with inhibitors targeting multiple pathways, including the epidermal growth factor receptor, encompassing dermatologic toxicities, diarrhea, hepatotoxicity, and interstitial lung disease. It also discusses the potential role of predictive biomarkers in identifying high-risk populations to facilitate early risk stratification. Furthermore, based on current evidence-based medicine and authoritative clinical guidelines, this work highlighted a multidisciplinary management strategy, tailored according to severity grading, which includes dose modification or treatment interruption, symptomatic and supportive care, as well as lifestyle interventions. Through a deepened understanding, proactive monitoring, and standardized management of ADRs, the aim is to maximize treatment benefits while minimizing therapy-related toxic burden.

1.Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4(1): 47-53. DOI: 10.1016/j.jncc.2024.01.006.

2.Riely GJ, Wood DE, Ettinger DS, et al. Non-small cell lung cancer, version 4.2024, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2024, 22(4): 249-274. DOI: 10.6004/jnccn.2204.0023.

3.Kujtan L, Subramanian J. Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer[J]. Expert review of anticancer therapy, 2019, 19(7): 547-559. DOI: 10.1080/14737140.2019.1596030.

4.Nakagawa K, Garon EB, Seto T, et al. RELAY: final overall survival for erlotinib plus ramucirumab or placebo in untreated, EGFR-mutated metastatic NSCLC[J]. J Thorac Oncol, 2025, 20(4): 487-499. DOI: 10.1016/j.jtho.2024.11.032.

5.Reungwetwattana T, Cho BC, Lee KH, et al. Lazertinib versus gefitinib tyrosine kinase inhibitors in treatment-naíve patients with EGFR-mutated advanced nSCLC: analysis of the Asian subpopulation in LASER301[J]. J Thorac Oncol, 2023, 18(10): 1351-1361. DOI: 10.1016/j.jtho.2023.06.016.

6.Zhou HQ, Zhang YX, Chen G, et al. Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial[J]. Signal Transduct Target Ther, 2024, 9(1): 215. DOI: 10.1038/s41392-024-01927-9.

7.Lu S, Zhou J, Jian H, et al. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study[J]. Lancet Respir Med, 2023, 11(10): 905-915. DOI: 10.1016/s2213-2600(23)00183-2.

8.NCI. Common Terminology Criteria for Adverse Events (CTCAE) v5.0[EB/OL]. (2017-11-27) [2025-08-29]. https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events#ctcae.

9.Ding PN, Lord SJ, Gebski V, et al. Risk of treatment-related toxicities from EGFR tyrosine kinase inhibitors: a Meta-analysis of clinical trials of gefitinib, erlotinib, and afatinib in advanced EGFR-mutated non-small cell lung cancer[J]. J Thorac Oncol, 2017, 12(4): 633-643. DOI: 10.1016/j.jtho.2016.11.2236.

10.Mok TS, Cheng Y, Zhou X, et al. Updated overall survival in a randomized study comparing dacomitinib with gefitinib as first-line treatment in patients with advanced non-small-cell lung cancer and EGFR-activating mutations[J]. Drugs, 2021, 81(2): 257-266. DOI: 10.1007/s40265-020-01441-6.

11.Cho JH, Lim SH, An HJ, et al. Osimertinib for patients with non-small-cell lung cancer harboring uncommon EGFR mutations: a multicenter, open-label, phase II trial (KCSG-LU15-09)[J]. J Clin Oncol, 2020, 38(5): 488-495. DOI: 10.1200/jco.19.00931.

12.Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J]. N Engl J Med, 2018, 378(2): 113-125. DOI: 10.1056/NEJMoa1713137.

13.Shalata W, Abu Jama A, Dudnik Y, et al. Adverse events in osimertinib treatment for EGFR-mutated non-small-cell lung cancer: unveiling rare life-threatening myelosuppression[J]. Medicina (Kaunas), 2024, 60(8): 1270. DOI: 10.3390/medicina 60081270.

14.Shi Y, Chen G, Wang X, et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study[J]. Lancet Respir Med, 2022, 10(11): 1019-1028. DOI: 10.1016/s2213-2600(22)00168-0.

15.Yang JC, Camidge DR, Yang CT, et al. Safety, efficacy, and pharmacokinetics of almonertinib (HS-10296) in pretreated patients with EGFR-mutated advanced NSCLC: a multicenter, open-label, phase 1 trial[J]. J Thorac Oncol, 2020, 15(12): 1907-1918. DOI: 10.1016/j.jtho.2020.09.001.

16.Yuankai S, Gongyan C, Xiang W, et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study[J]. Lancet Respir Med, 2022, 10(11): 1019-1028. DOI: 10.1016/s2213-2600(22)00168-0.

17.Xu Y, Chen M, Gao X, et al. Efficacy and safety of sunvozertinib monotherapy as first-line treatment in NSCLC patients with EGFR exon 20 insertion mutations: a phase 2, single-center trial[J]. Cancer Lett, 2025, 630: 217904. DOI: 10.1016/j.canlet.2025. 217904.

18.Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer[J]. N Engl J Med, 2014, 371(23): 2167-2177. DOI: 10.1056/NEJMoa1408440.

19.Nishio M, Kim DW, Wu YL, et al. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer[J]. Cancer Res Treat, 2018, 50(3): 691-700. DOI: 10.4143/crt.2017.280.

20.Yang J, Liu G, Lu S, et al. Brigatinib versus alectinib in ALK-positive NSCLC after disease progression on crizotinib: results of phase 3 ALTA-3 trial[J]. J Thorac Oncol, 2023, 18(12): 1743-1755. DOI: 10.1016/j.jtho.2023.08.010.

21.Yuan X, Wang Y, Yang M, et al. A retrospective study of ensartinib-treated ALK-positive locally advanced or metastatic NSCLC patients in China[J]. Lung Cancer Manag, 2023, 12(4): Lmt61. DOI: 10.2217/lmt-2023-0005.

22.Shaw A, Bauer T, de Marinis F, et al. ALKfirst-line lorlatinib or crizotinib in advanced -positive lung cancer[J]. The New England journal of medicine, 2020, 383(21): 2018-2029. DOI: 10.1056/NEJMoa2027187.

23.de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS(G12C) mutation: a randomised, open-label, phase 3 trial[J]. Lancet, 2023, 401(10378): 733-746. DOI: 10.1016/s0140-6736(23)00221-0.

24.Jänne P, Riely G, Gadgeel S, et al. Adagrasib in non-small-cell lung cancer harboring a mutation[J]. New Engl J Med, 2022, 387(2): 120-131. DOI: 10.1056/NEJMoa2204619.

25.Shi Y, Fang J, Xing L, et al. Glecirasib in KRAS(G12C)-mutated nonsmall-cell lung cancer: a phase 2b trial[J]. Nat Med, 2025, 31(3): 894-900. DOI: 10.1038/s41591-024-03401-z.

26.Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials[J]. Lancet Oncol, 2020, 21(4): 531-540. DOI: 10.1016/s1470-2045(19)30856-3.

27.Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials[J]. Lancet Oncol, 2020, 21(2): 271-282. DOI: 10.1016/s1470-2045(19)30691-6.

28.Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial[J]. Lancet Oncol, 2016, 17(7): 984-993. DOI: 10.1016/s1470-2045(16)30146-2.

29.Louisa L, Joshua S, Karen LR, et al. Emerging targets in non-small cell lung cancer[J]. Int J Mol Sci, 2024, 25(18): 10046. DOI: 10.3390/ijms251810046.

30.Li W, Xiong A, Yang N, et al. Efficacy and safety of taletrectinib in Chinese patients with ROS1+ non-small cell lung cancer: the phase II TRUST-I study[J]. J Clin Oncol, 2024, 42(22): 2660-2670. DOI: 10.1200/jco.24.00731.

31.Wolf J, Hochmair M, Han JY, et al. Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial[J]. Lancet Oncol, 2024, 25(10): 1357-1370. DOI: 10.1016/s1470-2045(24)00441-8.

32.Drilon A, Clark JW, Weiss J, et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration[J]. Nat Med, 2020, 26(1): 47-51. DOI: 10.1038/s41591-019-0716-8.

33.Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14-skipping non-small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial[J]. JAMA Oncol, 2023, 9(9): 1260-1266. DOI: 10.1001/jamaoncol.2023.1962.

34.Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations[J]. N Engl J Med, 2020, 383(10): 931-943. DOI: 10.1056/NEJMoa2004407.

35.Yu Y, Guo Q, Zhang Y, et al. Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study[J]. Lancet Respir Med, 2024, 12(12): 958-966. DOI: 10.1016/S2213-2600(24)00211-X.

36.Ferrara R, Auger N, Auclin E, et al. Clinical and translational implications of RET rearrangements in non-small cell lung cancer[J]. J Thorac Oncol, 2018, 13(1): 27-45. DOI: 10.1016/j.jtho.2017.10.021.

37.Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion-positive non-small-cell lung cancer: updated safety and efficacy from the registrational LIBRETTO-001 phase I/II trial[J]. J Clin Oncol, 2023, 41(2): 385-394. DOI: 10.1200/jco.22.00393.

38.Griesinger F, Curigliano G, Thomas M, et al. Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial[J]. Ann Oncol, 2022, 33(11): 1168-1178. DOI: 10.1016/j.annonc.2022.08.002.

39.Zhou C, Li X, Wang Q, et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase II study[J]. J Clin Oncol, 2020, 38(24): 2753-2761. DOI: 10.1200/jco.20.00297.

40.Guan S, Chen X, Chen Y, et al. FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy[J]. Acta Pharm Sin B, 2022, 12(9): 3639-3649. DOI: 10.1016/j.apsb.2022.02.006.

41.Mizugaki H, Hamada A, Shibata T, et al. Exploration of germline variants responsible for adverse events of crizotinib in anaplastic lymphoma kinase-positive non-small cell lung cancer by target-gene panel sequencing[J]. Lung Cancer, 2019, 128: 20-25. DOI: 10.1016/j.lungcan.2018.12.002.

42.Liao D, Liu Z, Zhang Y, et al. Polymorphisms of drug-metabolizing enzymes and transporters contribute to the individual variations of erlotinib steady state trough concentration, treatment outcomes, and adverse reactions in epidermal growth factor receptor-mutated non-small cell lung cancer patients[J]. Front Pharmacol, 2020, 11: 664. DOI: 10.3389/fphar.2020.00664.

43.Veerman GDM, Boosman RJ, Jebbink M, et al. Influence of germline variations in drug transporters ABCB1 and ABCG2 on intracerebral osimertinib efficacy in patients with non-small cell lung cancer[J]. EClinicalMedicine, 2023, 59: 101955. DOI: 10.1016/j.eclinm.2023.101955.

44.Hichert V, Scholl C, Steffens M, et al. Predictive blood plasma biomarkers for EGFR inhibitor-induced skin rash[J]. Oncotarget, 2017, 8(21): 35193-35204. DOI: 10.18632/oncotarget.17060.

45.Kemski S, Molitor V, Steffens M, et al. Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity[J]. Oncotarget, 2021, 12(10): 982-995. DOI: 10.18632/oncotarget.27953.

46.王可, 李娟, 孙建国, 等. 间变性淋巴瘤激酶抑制剂不良反应管理西南专家建议（2021年版）[J]. 中国肺癌杂志, 2021, 24(12): 815-828. [Wang K, Li J, Sun JG, et al. Recommendations from experts in the management of adverse reactions to ALK inhibitors(2021 Version)[J]. Chinese Journal of Lung Cancer, 2021, 24(12): 815-828.] DOI: 10.3779/j.issn.1009-3419.2021.102.32.

47.上海市抗癌协会癌症康复与姑息治疗专业委员会, 上海市抗癌协会肿瘤药物临床研究专业委员会, 中国老年保健协会肿瘤防治与临床研究管理专业委员会. 抗肿瘤治疗所致恶心呕吐全程管理上海专家共识（2024年版）[J]. 中国癌症杂志, 2024, 34(1): 104-134. [Cancer Rehabilitation and Palliative Professional Committee of Shanghai Anti-Cancer Association, Cancer Drug Clinical Research Committee of Shanghai Anti-Cancer Association, Cancer Prevention and Clinical Research Committee of Chinese Aging Well Association. Shanghai expert consensus on whole-process management of antineoplastic-induced nausea and vomiting (2024 edition)  [J]. China Oncology, 2024, 34(1): 104-134.] DOI: 10.19401/j.cnki.1007-3639.2024.01.008.

48.胡洁, 林丽珠, 骆肖群, 等. EGFR-TKI不良反应管理专家共识[J]. 中国肺癌杂志, 2019, 22(2): 57-81. [Hu J, Lin LZ, Luo XQ, et al. EGFR-TKI ADR management Chinese expert consensus[J]. Chinese Journal of Lung Cancer, 2019, 22(2): 57-81.] DOI: 10.3779/j.issn.1009-3419.2019.02.01.

49.茅益民. 《中国药物性肝损伤诊治指南（2023年版）》解读[J]. 中华肝脏病杂志, 2024, 32(4): 312-317. [Mao YM. Interpretation of the Chinese guideline for diagnosis and management of drug-induced liver injury (2023 version)[J]. Chinese Journal of Hepatology, 2024, 32(4): 312-317.] DOI: 10.3760/cma.j.cn501113-20230829-00077.

50.Balagula Y, Lacouture ME, Cotliar JA. Dermatologic toxicities of targeted anticancer therapies[J]. J Support Oncol, 2010, 8(4): 149-161. https://pubmed.ncbi.nlm.nih.gov/20822032/.

51.Califano R, Tariq N, Compton S, et al. Expert consensus on the management of adverse events from EGFR tyrosine kinase inhibitors in the UK[J]. Drugs, 2015, 75(12): 1335-1348. DOI: 10.1007/s40265-015-0434-6.

52.Nishio M, Kato T, Toyozawa R, et al. Management of peripheral edema in patients with MET exon 14-mutated non-small cell lung cancer treated with small molecule MET inhibitors[J]. Target Oncol, 2022, 17(5): 597-604. DOI: 10.1007/s11523-022-00912-y.

53.Federico C, Denis MS, Oliver G, et al. Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus[J]. Lung Cancer, 2015, 87(2): 89-95. DOI: 10.1016/j.lungcan.2014.12.010.

54.Heinzerling L, Eigentler TK, Fluck M, et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management[J]. ESMO Open, 2019, 4(3): e000491. DOI: 10.1136/esmoopen-2019-000491.

55.潘炽星, 李紫韵, 陈纯波. 血清镁在急性肾损伤诊疗中的研究进展[J]. 医学新知, 2024, 34(6): 707-716. [Pan CX, Li ZY, Chen CB. Research progress of serum magnesium in the diagnosis and treatment of acute kidney injury[J]. Yixue Xinzhi Zazhi, 2024, 34(6): 707-716.] DOI: 10.12173/j.issn.1004-5511.202403045.