In recent years, antibody-drug conjugates(ADC) have become an important part of cancer treatment. A new favorite. The so-called ADC drug is to carry cytotoxic drugs onto monoclonal antibodies and deliver them to cancer cells precisely, like a precision-guided missile designed to bombard cancer cells. Since the first ADC drug T-DM1 was approved for marketing in 2013, many new ADC drugs have left a strong mark in the treatment of cancer, like breaking Goxatuzumab et al. In addition to breast cancer, ADC drugs are also entering other cancers. For example, goxatuzumab achieved an objective response rate of 27.4% and a clinical benefit rate of 37.2% in patients with advanced urothelial carcinoma who had received platinum and PD-(L)1 therapy< span>[1] and FDA-approved in April 2021 for the treatment of advanced urothelial cancer. And Chinese urothelial cancer patients will soon be able to use this kind of “magic medicine”. Recently, a number of well-known domestic experts jointly released the Consensus on the Safety of Clinical Application of Urothelial Carcinoma Antibody Conjugates (First Edition) , which outlines in detail the adverse reactions and matters needing attention of various ADC drugs in the treatment of urothelial carcinoma, paving the way for the application of ADC drugs in China. 
ADC drug goxatuzumab has been approved in China >1Which ADC drugs are involved< /span>A total of 3 ADC drugs for urothelial carcinoma were included in the “Consensus”. In addition to the most well-known goxatuzumab, there are Enfortumab Vedotin(EV)and domestically producedVidicilumab. The cytotoxic payload of the latter two ADC drugs is the microtubule inhibitor MMAE, and the targets they target are different. Ennozumab is an ADC drug targeting nectin-4 molecule. Since nectin-4 is widely distributed in urothelial carcinoma, ennozumab also does not need to detect nectin-4 expression in patients before use. In patients with advanced urothelial carcinoma treated with platinum and PD-(L)1, ennozumab reduced disease by 38% compared to chemotherapy Risk of progression and 30% risk of death, objective response rate 40.6%[3]< span>. Veldicitumab targets the HER2 molecule. Vidicitumab achieved an objective response rate of 51.2% in previously treated HER2-positive urothelial carcinoma[4 ].
2 strong>Precautions for ADC drug infusionAll ADC drugs are macromolecular drugs. It needs to be administered by intravenous infusion, and infusion reactions may occur during the infusion. Infusion reaction refers to an allergic or anaphylactoid reaction caused by a drug during infusion. The main manifestations include fever, dizziness, vomiting, etc. In severe cases, it can lead to coma or even death.[5]. In the event of an infusion reaction, the infusion should be stopped in time, and glucocorticoids, antihistamines, and diphenhydramine should be used for symptomatic treatment. After symptoms have resolved, patients with milder reactions can slow the infusion rate under close monitoring and try to resume dosing. These drugs may also be used before infusion to prevent infusion reactions. In addition, anti-cancer treatment is a slow process, and many patients have to inject drugs repeatedly over a long period of time. Conditional patients can choose to use a deep venous catheter or implant an venous infusion port for administration to avoid local risks during infusion such as drug extravasation.
For neutropenia, you can Temporarily discontinue the drug, use antibiotics to prevent infection, and use white blood-raising drugs to increase white blood cells;
For anemia, blood transfusion or drug support can be used; span>
For diarrhea, anti-diarrheal drugs such as Yimeng can be used to stop diarrhea;
- < span>For nausea and vomiting, antiemetic drugs such as metoclopramide can be used to prevent and manage it.
Note What is more, diarrhea that occurs within 24 hours after infusion of goxatuzumab is mostly caused by cholinergic nerve excitation, and may be accompanied by symptoms such as drooling, sweating, bradycardia, and hyperperistalsis. Spontaneous relief, if necessary, can also be treated with atropine.
4EV and Vidicitumab< /span>Beware of Peripheral Neuropathy and DysglycemiaEV and Vidicitumumab The cytotoxic loads carried are all MMAE, which also makes the adverse reactions of the two more similar, with more neurological and metabolic-related adverse reactions. Both types of adverse reactions were relatively rare in patients treated with goxatuzumab. In clinical trials, the incidence of peripheral neuropathy was 33.8%, 14%, and 4% for EV, vedicetuzumab, and goxatuzumab, respectively. The incidence of elevated blood glucose was 14%, 11.6%, and <1%, respectively. In addition, 60.5% of the patients taking vellicitumab experienced dysesthesia, and 23.3% experienced an increase in blood triglycerides. In addition, EV and vedicitumab may also have autonomic toxicity and can induce paralytic ileus. Bowel obstruction occurred in approximately 5.3% of patients treated with vellicitumab. Once the patient develops intestinal obstruction, it is necessary to stop the drug in time, perform an enema for defecation, and continue the treatment after the intestinal function is restored.
peripheral neuropathy Allergies, muscle cramps or weakness, etc.5EV – Special attention should be paid to skin and ocular toxicityThe nectin-4 molecule targeted by EV is not only present in cancer cells, but also in skin. and cornea, which also lead to frequent skin and ocular adverse effects of EV. Approximately 43.9% of EV-treated patients experienced adverse skin reactions, including rash, itching, dry skin, and maculopapular rash; 20.3% experienced severe adverse skin reactions Development, including bullous dermatitis, exfoliative dermatitis, etc., can even lead to toxic epidermal necrosis syndrome. In contrast, approximately 6% of goxatuzumab-treated patients developed rash, and approximately 16.3% of vellicitumab-treated patients developed pruritus, both mild. In terms of ocular toxicity, the incidence of ocular diseases caused by EV is about 40%, including keratitis, blurred vision, increased lacrimation, conjunctivitis and dry eye. Careful monitoring of ocular conditions should be exercised when using EV, and treatment with artificial tears and topical steroids should be used if necessary. EVs should be avoided in patients with active keratitis or corneal ulcers.
References:[1]. Tagawa S T, Balar A V, Petrylak D P, et al. TROPHY-U-01: A
phase IIopen-label study of sacituzumab govitecan in patients with metastatic
urothelial carcinoma progressing after platinum-based chemotherapy and
checkpoint inhibitors[J]. Journal of Clinical Oncology, 2021, 39(22):
2474-2485.[2]. Consensus on the safety of clinical application of antibody-drug conjugates in urothelial carcinoma (first edition)[J/OL].Modern Urology:1-7[2022-07 -29].http://kns.cnki.net/kcms/detail/61.1374.R.20220614.1711.002.html[3]. Powles T, Rosenberg J E, Sonpavde G P, et al. Enfortumab
vedotin in previously treated advanced urothelial carcinoma[J]. New England
Journal of Medicine, 2021, 384(12): 1125-1135.[4]. Sheng X, Yan X, Wang L, et al. Open-label, Multicenter, Phase
II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients
with Locally Advanced or Metastatic Urothelial CarcinomaA Phase II Study of
RC48-ADC in Advanced Urothelial Carcinoma[J]. Clinical Cancer Research, 2021,
27(1): 43-51.[5]. Vogel W H. Infusion reactions: diagnosis, assessment, and
management[J]. Clinical journal of oncology nursing, 2010, 14(2): E10.