Inetetamab for Injection

Function and indication:
Ceptin (Initutumab for injection) is suitable for HER2-positive metastatic breast cancer: combined with vinorelbine for the treatment of patients with metastatic breast cancer who have received one or more chemotherapy regimens.
Usage and dosage:
HER2 detection Before using this product for treatment, HER2 status should be tested. This product can be used for patients with positive immunohistochemistry (IHC) test results (+++) or suspected positive immunohistochemistry test results (++) and positive fluorescence in situ hybridization (FISH) test results. Recommended dose and administration method The recommended initial loading dose of Initutumab is 4 mg/kg, intravenous infusion for more than 90 minutes; the maintenance dose is 2 mg/kg, once a week. If the patient tolerates well during the first infusion, the subsequent infusion can be changed to 30 minutes. Intravenous push or rapid intravenous injection is strictly prohibited. The recommended dose of vinorelbine is 25 mg/m2, intravenous infusion on days 1, 8, and 15, and applied on the day after Initutumab infusion, and every 28 days is a cycle. For detailed information on the use of vinorelbine, please refer to the drug instructions for vinorelbine. Dose adjustment Infusion-related reactions Patients with mild to moderate infusion-related reactions can reduce the infusion rate; the infusion should be interrupted when dyspnea or clinically significant hypotension occurs; patients with severe and life-threatening infusion-related reactions should permanently stop using this product. Cardiotoxicity 3/13 The left ventricular ejection fraction (LVEF) should be tested before starting treatment with this product, and LVEF should also be routinely monitored during treatment. If the absolute value of LVEF decreases by more than 10% compared with the absolute value before treatment and the absolute value of LVEF decreases to less than 50%, treatment with this product should be suspended for at least 3 weeks. If the LVEF rises to ≥50% or decreases by ≤10% compared with the absolute value before treatment within 3 weeks, this product can be resumed; if the LVEF does not improve or further decreases, or clinically significant congestive heart failure occurs, this product should be discontinued. Instructions for use This product does not contain any preservatives, and the preparation of the solution and intravenous infusion process should comply with the principles of aseptic operation. First, add 2.5ml sterile water for injection to each vial of this product, gently rotate to dissolve; calculate the dosage according to the patient’s weight, draw the required volume of solution, slowly inject 250ml 0.9% sodium chloride injection (do not use 5% glucose injection), gently turn over and mix, and then drip intravenously. Violent shaking is strictly prohibited! The prepared solution is a colorless to slightly yellow transparent solution. To prevent microbial contamination, the drug solution should be used immediately after dissolution. Before dripping the solution, visually check for particle generation and/or discoloration
Adverse reactions:
Overview of safety characteristics Approximately 369 patients with metastatic breast cancer received inituzumab monotherapy or combination therapy in clinical trials. The safety data of inituzumab combined with vinorelbine for HER2-positive metastatic breast cancer mainly come from two clinical trials: a phase II clinical trial conducted in 109 patients with metastatic breast cancer who had previously received chemotherapy (72 of whom used inituzumab combined with vinorelbine); and a phase III clinical trial conducted in 341 patients with metastatic breast cancer who had previously received chemotherapy (225 of whom used inituzumab combined with vinorelbine). The most common adverse reactions in the treatment of metastatic breast cancer with inituzumab combined with vinorelbine include neutropenia, leukopenia, anemia, fever, chills, nausea, vomiting, and elevated transaminases. Grade 3 or higher adverse reactions with an incidence of >2% include neutropenia, leukopenia, anemia, and thrombocytopenia. Compared with the vinorelbine monotherapy group, adverse reactions with a higher incidence in the initutuzumab combined with vinorelbine treatment group included fever, chills, anemia, and elevated transaminases, most of which were mild adverse events of grade 1 to 2; the higher incidence of grade 3 to 4 adverse reactions was neutropenia and leukopenia. List of adverse reactions A randomized, open, controlled Phase III clinical study compared the safety and efficacy of initutuzumab combined with vinorelbine versus vinorelbine in the treatment of HER2-positive recurrent or metastatic breast cancer that had previously received one or more chemotherapy regimens. Table 1 lists the adverse reactions with an incidence of ≥ 1% in the trial group during the treatment of this study. (See the instructions for the table) Cardiac toxicity The cardiac-related adverse reactions reported in this Phase III clinical trial were abnormal electrocardiograms and palpitations, and no symptomatic cardiac toxicity events were observed. The incidence of cardiac-related adverse reactions was 7.11% and 5.61% in the trial group and control group, respectively, all of which were mild reactions, and there was no statistically significant difference between the groups. In clinical trials of trastuzumab, a similar anti-HER2 monoclonal antibody, patients receiving trastuzumab alone or chemotherapy containing anthracyclines (doxorubicin or epirubicin) followed by trastuzumab combined with taxanes were observed to experience cardiotoxicity, including left ventricular dysfunction, arrhythmias, hypertension, symptomatic heart failure, cardiomyopathy, and cardiac death. Congestive heart failure (NYHA grade II-IV) is a common adverse reaction to trastuzumab and can lead to fatal consequences. The incidence of cardiac dysfunction caused by trastuzumab alone in patients with metastatic breast cancer is 6-9%; when trastuzumab is combined with anthracycline antibiotics/cyclophosphamide chemotherapy, the incidence of cardiac dysfunction is 27%, which is significantly higher than that of patients using only anthracycline antibiotics/cyclophosphamide (7-10%). At present, there is limited data on long-term exposure of a large number of people to inituzumab, but cardiotoxicity is related to its HER2 target, which should also be paid attention to in the use of this product. Infusion-related reactions In this Phase III clinical trial, fever and chills associated with inutuzumab infusion were the two most common adverse reactions in “systemic diseases and various reactions at the administration site”, and the overall incidence rates were significantly different between the experimental group and the control group (fever: 36.44% vs. 10.28%; chills: 15.56% vs. 0.93%). The vast majority of inutuzumab-related infusion reactions were mild reactions of grade 1 to 2, which were easily tolerated, and the symptoms disappeared after symptomatic treatment or without treatment, and generally had no effect on the patient’s subsequent use of drugs. Hematological toxicity Hematological toxicity was uncommon in patients receiving trastuzumab monotherapy, with the incidence of World Health Organization (WHO) grade 3 leukopenia, thrombocytopenia, and anemia less than 1%, and no WHO grade 4 toxicity was observed. In the clinical trial of initutuzumab combined with vinorelbine for the treatment of metastatic breast cancer, common adverse reactions of the blood system included neutropenia, leukopenia, anemia, bone marrow suppression, thrombocytopenia, etc. The incidence of grade 3 or 4 hematological toxicity in the combined treatment group was higher than that in the vinorelbine monotherapy group (the incidence of grade 3/4 neutropenia was 71.11% vs. 53.27%; the incidence of grade 3/4 leukopenia was 60.44% vs. 45.79%); the incidence of anemia in the combined treatment group and the vinorelbine monotherapy group was 56.89% and 36.45%, respectively, and the incidence of grade 3/4 anemia was 7.56% and 6.54%, respectively. Compared with vinorelbine monotherapy, the incidence of elevated transaminases in patients treated with initutuzumab combined with vinorelbine was higher (8.41% vs. 15.11%), but it was basically mild abnormality of grade 1~2. Infections In the clinical trial of inituzumab combined with vinorelbine for the treatment of metastatic breast cancer, the overall incidence of infection was 9.33%, higher than that of patients using chemotherapy alone (4.67%). The most common sites of infection were the respiratory tract and urinary tract. Diarrhea The incidence of diarrhea in patients receiving inituzumab combined with vinorelbine chemotherapy was higher than that in patients receiving chemotherapy alone (2.67% vs 0.93%). Immunogenicity Immunogenicity studies were not conducted in this Phase III trial, and the immunogenicity of this product will be evaluated after marketing.
Contraindications:
It is contraindicated in patients with known allergies to any component of this product or proteins expressed by Chinese hamster ovary cells.