Treatment of antibody-drug conjugates in elderly patients

doi:10.16352/j.issn.1001-6325.2025.10.1270

Abstract

Abstract: Antibody-drug conjugates(ADCs) are emerging anti-cancer drugs that have been widely applied in the treatment of hematological and solid tumors. ADCs deliver cytotoxic drugs to tumor cells with precision through antibody targeting, enhancing efficacy while reducing side effects. Elderly cancer patients face treatment challenges due to factors such as drug metabolism, multiple comorbidities and decreased physical function. However, ADCs have therapeutic advantages in elderly patients. The article discusses the efficacy, safety, dosing strategies, and adverse reaction management of ADCs in elderly patients, in order to provide effective and safe treatment options for elderly cancer patients.

Key words: antibody-drug conjugates, elder patients, cancer treatment, targeted therapy

CLC Number:

R730.5

LIU Fengshuo, GUAN Mei. Treatment of antibody-drug conjugates in elderly patients[J]. Basic & Clinical Medicine, 2025, 45(10): 1270-1276.

References 35

[1]	Dumontet C, Reichert JM, Senter PD, et al. Antibody-drug conjugates come of age in oncology[J]. Nat Rev Drug Discov, 2023,22:641-661. doi:10.1038/s41573-023-00709-2.
[2]	Strebhardt K, Ullrich A. Paul Ehrlich's magic bullet concept: 100 years of progress[J]. Nat Rev Cancer, 2008,8:473-480. doi:10.1038/nrc2394.
[3]	Tarantino P, Carmagnani Pestana R, Corti C, et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies[J]. CA Cancer J Clin, 2022,72:165-182. doi:10.3322/caac.21705.
[4]	McPherson MJ, Hobson AD. Pushing the envelope: advancement of ADCs outside of oncology[J]. Methods Mol Biol, 2020,2078:23-36. doi:10.1007/978-1-4939-9929-3_2.
[5]	Xi M, Zhu J, Zhang F, et al. Antibody-drug conjugates for targeted cancer therapy: recent advances in potential payloads[J]. Eur J Med Chem, 2024,276:116709. doi:10.1016/j.ejmech.2024.116709
[6]	Van Herck Y, Feyaerts A, Alibhai S, et al. Is cancer biology different in older patients?[J]. Lancet Healthy Longev, 2021,2:e663-e677. doi:10.1016/S2666-7568(21)00179-3.
[7]	Sedrak MS, Freedman RA, Cohen HJ, et al. Older adult participation in cancer clinical trials: a systematic review of barriers and interventions[J]. CA Cancer J Clin, 2021,71:78-92. doi:10.3322/caac.21638.
[8]	Rached L, Geraud A, Frelaut M, et al. Antibody drug conjugates in older patients: state of the art[J]. Crit Rev Oncol Hematol, 2024,193:104212. doi:10.1016/j.critrevonc.2023.104212.
[9]	白婉婷,扈金萍. 抗体偶联药物的药代动力学特征及其在消化道系统癌症治疗中的研究进展[J]. 药学学报, 2023,58: 2632-2639. doi:10.16438/j.0513-4870.2023-0019.
[10]	McCarthy C, Flood M, Clyne B, et al. Medication changes and potentially inappropriate prescribing in older patients with significant polypharmacy[J]. Int J Clin Pharm, 2023,45:191-200. doi:10.1007/s11096-022-01497-2.
[11]	McCarthy C, Clyne B, Corrigan D, et al. Supporting prescribing in older people with multimorbidity and significant polypharmacy in primary care (SPPiRE): a cluster randomised controlled trial protocol and pilot[J]. Implement Sci, 2017,12:99. doi:10.1186/s13012-017-0629-1.
[12]	Hossain N, Prashad M, Huszti E, et al. Age-related differences in symptom distress among patients with cancer[J]. J Geriatr Oncol, 2023, 14:101601. doi:10.1016/j.jgo.2023.101601.
[13]	Gammelgaard OL, Guldberg P, Gjerstorff MF, et al. Age-related differences in cancer biology in older patients[J]. Ugeskr Laeger, 2024,186:V06230375. doi:10.61409/V06230375.
[14]	DeSantis CE, Miller KD, Dale W, et al. Cancer statistics for adults aged 85 years and older, 2019[J]. CA Cancer J Clin, 2019,69:452-467. doi:10.3322/caac.21577.
[15]	Mohile SG, Fan L, Reeve E, et al. Association of cancer with geriatric syndromes in older medicare beneficiaries[J]. J Clin Oncol, 2011,29:1458-1464. doi:10.1200/JCO.2010.31.6695.
[16]	余夫,郭宏, 仝慧娟.老年肺癌患者化疗前后焦虑及抑郁现状分析[J].沈阳医学院学报, 2024,24:613-616.doi:10.16753/j.cnki.1008-2344.2024.06.009.
[17]	Korotkin BD, Hoerger M, Voorhees S, et al. Social support in cancer: how do patients want us to help?[J]. J Psychosoc Oncol, 2019,37:699-712. doi:10.1080/07347332.2019.1580331.
[18]	Liu K, Li M, Li Y, et al. A review of the clinical efficacy of FDA-approved antibody-drug conjugates in human cancers[J]. Mol Cancer, 2024, 23:62. doi:10.1186/s12943-024-01963-7.
[19]	中国抗癌协会肿瘤药物临床研究专业委员会,国家抗肿瘤药物临床应用监测专家委员会,国家肿瘤质控中心乳腺癌专家委员会,等. 抗体药物偶联物治疗恶性肿瘤临床应用中国专家共识(2023版)[J]. 中华肿瘤杂志,2023, 45:741-762. doi: 10.3760/cma.j.cn112152-20220713-00489.
[20]	Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer[J]. N Engl J Med, 2021,384:1529-1541. doi:10.1056/NEJMoa2028485.
[21]	Krop IE, Wildiers H, Hurvitz SA, et al. An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03[J].J Clin Oncol, 2023, 41 (Suppl 16),1006. doi:10.1200/JCO.2023.41.16_suppl.1006
[22]	Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma[J]. N Engl J Med, 2021, 384:1125-1135. doi:10.1056/NEJMoa2035807
[23]	Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage Ⅲ or Ⅳ Hodgkin's lymphoma[J]. N Engl J Med, 2018,378:331-344. doi:10.1056/NEJMoa1708984.
[24]	Tucci A, Martelli M, Rigacci L, et al. Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation(FIL)[J]. Leuk Lymphoma, 2015, 56: 921-926. doi: 10.3109/10428194.2014.953142.
[25]	Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B- cell lymphoma[J]. N Engl J Med, 2022, 386:351- 363. doi: 10.1056/NEJ Moa2115304.
[26]	Suri A, Mould DR, Song G, et al. Population pharmacokinetic modeling and exposure-response assessment for the antibody-drug conjugate brentuximab vedotin in Hodgkin's lymphoma in the phase Ⅲ ECHELON-1 study[J]. Clin Pharmacol Ther, 2019,106:1268-1279. doi:10.1002/cpt.1530.
[27]	Gouliaev A, Berg J, Bibi R, et al. Multi-disciplinary team meetings for lung cancer in Norway and Denmark: results from national surveys and observations with MDT-MODe[J]. Acta Oncol, 2024,63:678-684. doi:10.2340/1651-226X.2024.40777.
[28]	Zhu Y, Liu K, Wang K, et al. Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis[J]. Cancer, 2023,129:283-295.
[29]	Nguyen TD, Bordeau BM, Balthasar JP. Mechanisms of ADC toxicity and strategies to increase ADC tolerability[J]. Cancers (Basel), 2023,15:713. doi: 10.3390/cancers15030713.
[30]	Pondé NF, Lambertini M, de Azambuja E. Twenty years of anti-HER2 therapy-associated cardiotoxicity[J]. ESMO Open, 2016,1:e000073.doi: 10.1136/esmoopen-2016-000073.
[31]	中国抗癌协会癌症康复与姑息治疗专业委员会,中国抗癌协会肿瘤临床化疗专业委员会,中国抗癌协会肿瘤支持治疗专业委员会,等.中国抗肿瘤治疗相关恶心呕吐预防和治疗指南(2023版)[J].中华肿瘤杂志, 2024, 46:481-501.
[32]	Masters JC, Nickens DJ, Xuan D, et al. Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads[J]. Invest New Drugs, 2018,36:121-135. doi:10.1007/s10637-017-0520-6.
[33]	Zhang L, Yan Y, Gao Y, et al. Antibody-drug conjugates and immune checkpoint inhibitors in cancer treatment: a systematic review and meta-analysis[J]. Sci Rep, 2024,14:22357. doi:10.1038/s41598-024-68311-z.
[34]	Lacouture ME, Sibaud V, Gerber PA, et al. Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines[J]. Ann Oncol, 2021,32:157-170. doi:10.1016/j.annonc.2020.11.005.
[35]	Stagg NJ, Shen BQ, Brunstein F, et al. Peripheral neuropathy with microtubule inhibitor containing antibody drug conjugates: Challenges and perspectives in translatability from nonclinical toxicology studies to the clinic[J]. Regul Toxicol Pharmacol, 2016, 82:1-13. doi:10.1016/j.yrtph.2016.10.012.