8 ADC drugs, the main points of clinical use at a glance

Antibody-drug conjugate (ADC) is a type of targeted biopharmaceutical that couples a target-specific monoclonal antibody with a highly lethal cytotoxic drug through a specific connector.
As a carrier, small molecule cytotoxic drugs can be efficiently transported to target tumor cells in a targeted manner.

Therefore, ADC drugs have been one of the hot research directions in the field of tumor precision therapy in recent years.

At present, 8 ADC drugs have been approved for clinical use in the world (including the fields of hematological tumors and solid tumors, Table 1).

Table 1 ADC drug names approved for clinical use Indications Domestic marketed ADC drug enmetrastuzumab (T-DM1) second-line treatment of HER-2 positive advanced breast cancer; anti-HER-2 neoadjuvant therapy Adjuvant treatment of breast cancer with residual lesions after Vibutuximab (BV) classic Hodgkin’s lymphoma; systemic anaplastic large cell lymphoma or CD30-positive peripheral T-cell lymphoma; primary CD30 skin Degenerative large cell lymphoma or CD30-positive grass-like granulomas, other ADC drugs that have been approved by the US FDA, polatuzumab vedotin (PV), combined with bendamustine and rituximab, for the treatment of refractory or relapsed diffuse large B-cell lymphoma The tumor trastuzumab deruxtecan (TD) has previously received ≥2 anti-HER-2 therapies, unresectable or metastatic HER-2 positive breast cancer sacituzumab govitecan (SG) has received at least second-line treatment for metastatic triple-negative breast cancer GO) CD33-positive acute myeloid leukemia inotuzumab ozogamicin (IO) adult relapsed or refractory CD22-positive precursor B-cell acute lymphoblastic leukemia enfortumab vedotin (EV) has previously received platinum-containing chemotherapy and 1 PD-1/L1 inhibition Locally advanced or metastatic urothelial cancer treated with drugs.

As antibodies and cytotoxic drugs are different, the adverse reactions of different ADC drugs are also different.

During medication, the corresponding adverse reactions should be closely monitored, and the adverse reactions that may have serious consequences should be actively prevented or given supportive treatment; when adverse symptoms are suspected to occur, pay close attention and timely diagnosis, and provide corresponding treatment plans after determining the occurrence of adverse reactions.
Adjust the drug treatment plan, carry out delayed treatment or reduce the amount of treatment, and stop the drug in time for serious adverse reactions; for difficult-to-handle adverse reactions, timely multidisciplinary consultations should be carried out to explore solutions.

Table 2 Common ADC drug-related adverse reactions and precautions Adverse reactions Precautions for hematological adverse reactions Perform a complete blood count check before the application of ADC drugs.
Patients who do not meet the treatment requirements should take the drugs carefully, and wait until the blood indicators return to normal or receive supportive treatment.
Medicine can be used after normal.Regularly monitor blood cell counts during treatment, and consider preventive medications for secondary prevention.

For patients with related risks of infusion reactions, corticosteroids, acetaminophen and/or diphenhydramine should be used in advance to minimize the risk of IRR.

During the infusion and at least 1 hour after the end of the infusion, monitor whether any infusion reactions occur.

For patients with infusion reactions, the infusion can be interrupted in time, and steroid hormones or antihistamines can be given symptomatic treatment; for patients with severe infusion reactions, it is recommended to permanently stop the drug.

Peripheral neuropathy: When severe peripheral neuropathy (Grade 3) occurs during ADC treatment, if the patient is unable to walk due to limb weakness and needs to be assisted by tools to walk, or due to limb numbness and pain, medical treatment for neuralgia Later, the quality of life is still severely affected, and when life is difficult, ADC treatment should be suspended; if symptoms improve and the patient is able to take care of himself, consider restarting treatment and adjust the ADC dose to a lower level; if more serious conditions occur Neuropathy (Grade 4), when the patient’s life is endangered, ADC treatment should be terminated immediately.

Hepatotoxicity: Perform liver function tests routinely and promptly intervene when abnormal liver function occurs.
During pulmonary toxicity, patients are advised to report immediately when they develop cough, dyspnea, fever, and/or any new worsening respiratory symptoms.
At the same time, pay close attention to whether the patient has the symptoms, signs and imaging changes of interstitial lung disease, and find evidence of interstitial lung disease in time.
Patients with suspicious interstitial lung disease should consult the respiratory department.

For asymptomatic (grade 1) interstitial lung disease, steroid corticosteroid therapy should be considered (such as ≥0.
5mg/kg prednisolone or other hormones of the same dose and titer), and treatment can be continued.

If symptomatic (grade 2 or higher) interstitial lung disease occurs, steroid corticosteroid therapy (such as ≥1mg/kg prednisolone or other hormones of the same dose and titer) should be started immediately.

After stable symptom control and imaging suggest that the absorption of lung shadows improves, the dose of corticosteroids should be gradually reduced to maintain a relatively long course of treatment (such as 4 weeks).

Patients who are diagnosed with symptomatic (grade 2 or higher) interstitial lung disease should permanently discontinue the drug.

If symptoms continue to worsen, it is recommended that multidisciplinary consultations and active interventions be made to prevent the development of a fatal outcome.

Gastrointestinal Adverse Reactions Gastrointestinal reactions are common adverse reactions of ADC drugs, including nausea, vomiting, and diarrhea.
They are usually mild.
If severe gastrointestinal reactions occur, they need to be closely monitored and actively handled.

Cardiotoxicity Cardiotoxicity is a common toxicity of anti-HER-2 drugs, usually manifested as a decrease in left ventricular ejection fraction (LVEF).

Before applying TD and T-DM1, patients should be fully evaluated, including personal and family history, adequate correction of cardiovascular disease and other risk factors, standard treatment of combined basic cardiovascular disease, recording of baseline ECG and echocardiogram, past acceptance Patients who have been treated with anthracyclines need to measure baseline troponin and natriuretic peptides.

During treatment, ECG and echocardiography should be reviewed regularly, and if necessary, the detection of myocardial markers such as brain natriuretic peptide or N-terminal brain natriuretic peptide, cardiac troponin I or high-sensitivity troponin should be perfected.

Objectively evaluate the risk of cardiac function and related cardiotoxic events, early detection, timely diagnosis and treatment.

For patients with baseline hypertension, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists and β-receptor blockers are the first choice for antihypertensive drugs.

For patients with asymptomatic cardiac insufficiency, please consult a cardiovascular specialist.
On the basis of taking angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists and β-receptor blockers, ADC drugs can be continued Treat and increase the frequency of LVEF monitoring (such as once every 4 weeks).
If the absolute value of LVEF is less than 50% (decrease ≥16%), or it is in the normal range but the LVEF declines ≥10% during treatment, ADC drug treatment should be suspended.
Angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist and β-receptor blocker were also given, and LVEF was reviewed within 3 to 4 weeks, and treatment was performed after LVEF returned to normal.

If the LVEF reduction is irreversible or severely reduced, or symptomatic congestive heart failure occurs, the drug should be permanently discontinued.
If necessary, consult a cardiovascular specialist and refer to the Chinese Society of Clinical Oncology "Anthracycline Cardiotoxicity Prevention Guidelines (2020) The standard procedures recommended by the guidelines include the timely diagnosis and treatment of heart failure. References: 1.
Chinese Anti-Cancer Association Cancer Drug Clinical Research Professional Committee, National Anti-Cancer Drug Clinical Application Monitoring Expert Committee, National Cancer Quality Control Center Breast Cancer Expert Committee, etc.
Expert consensus on the clinical application of antibody-drug conjugates in the treatment of malignant tumors (2020 edition) [J].
Chinese Journal of Medical Frontiers (Electronic Edition), 2021, 13(1): 1-15.