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Trastuzumab BS 60mg,150mg NK for intravenous infusion. Long-term specific use results survey targeting gastric cancer patients with confirmed HER2 overexpression. (/)

Trastuzumab BS Specific Use Results Survey (/)

172

The subjects were gastric cancer patients with confirmed HER2 overexpression. Gender-wise, 76.0% (130/171 cases) were male and 24.0% (41/171 cases) were female, and there were no pregnant cases. By age, the largest group was 70 to 80 years old, accounting for 39.8% (68/171 cases), while the proportion of elderly people aged 65 years or older was 70.2% (120/171 cases), and there were no cases of children under 15 years old. The BMI of patients with a BMI of less than 18.5 kg/m2 accounted for 26.9% (46/171 cases), and 7.0% (12/171 cases) had a BMI of 25.0 kg/m2 or greater. Regarding the presence or absence of a medical history, 48.0% (82/171 cases) reported a positive history. Of these, cardiac dysfunction accounted for 0.6% (1/171 cases), and pulmonary dysfunction for 2.3% (4/171 cases). Regarding the presence or absence of complications, 84.2% (144/171 cases) reported a positive history. Of these, cardiac dysfunction accounted for 9.4% (16/171 cases), pulmonary dysfunction for 16.4% (28/171 cases), hepatic dysfunction for 7.6% (13/171 cases), and renal dysfunction for 5.3% (9/171 cases). Regarding the presence or absence of allergic predispositions, 12.9% (22/171 cases) reported a positive history. The primary site at initial consultation was the stomach in 86.0% (147/171 cases) and the esophagogastric junction in 14.0% (24/171 cases). Regarding surgical resection of the primary lesion at initial consultation, no resection was performed in 66.1% (113/171 cases), curative resection in 26.9% (46/171 cases), and non-curative resection in 7.0% (12/171 cases). The main histological types were tubular adenocarcinoma in 69.6% (119/171 cases) and poorly differentiated adenocarcinoma in 38.6% (66/171 cases). The disease stage was stage IV in 71.9% (123/171 cases) and stage III in 16.4% (28/171 cases). At the time of enrollment, the primary disease status was unresectable progression in 70.2% (120/171 cases) and recurrence in 29.8% (51/171 cases). Furthermore, 99.4% (170/171 cases) of cases had metastasis at the time of enrollment, with the main metastatic sites being lymph nodes in 67.8% (116/171 cases), liver in 45.6% (78/171 cases), peritoneum in 25.1% (43/171 cases), and lung in 17.0% (29/171 cases). HER2 status was positive in all cases except for three cases in which IHC +2 and ISH had not been performed. P.S. was 0 in 57.3% (98/171 cases) and 1 in 38.6% (66/171 cases). Chemotherapy was administered as a previous treatment in 52.6% (90/171 cases), of which 11.7% (20/171 cases) had included chemotherapy using trastuzumab.

This study targeted gastric cancer patients with confirmed HER2 overexpression, with a target case count of 150, and was conducted using a central registration method from August 20, 2018 to August 31, 2023 (5 years), with a registration period from August 20, 2018 to August 31, 2022 (4 years) and an observation period of 1 year. During the registration period, contracts were signed with 71 facilities and 91 departments, and 172 cases were registered from 46 facilities and 51 departments. All survey forms were collected from 172 registered cases. Of these, 171 cases were selected for safety evaluation, excluding one case in which administration of this drug was initiated outside the contract period after the survey form was collected. In addition, of the safety evaluation cases, 3 cases in which HER2 testing was 2+ by IHC but ISH was not performed, so HER2 positivity could not be confirmed, leaving 168 cases for efficacy evaluation.

A total of 397 adverse reactions occurred in 115 patients, with the incidence rate of adverse reactions being 67.25% (115/171 patients). The most common adverse reactions, occurring five or more times, were anemia (26 cases), diarrhea (23 cases), nausea, decreased neutrophil count, and decreased white blood cell count (19 cases each), decreased appetite and decreased platelet count (18 cases each), constipation, fatigue, and increased aspartate aminotransferase (15 cases each), peripheral neuropathy and fever (12 cases each), and stomatitis and chills (10 cases each).There were 10 cases of stomatitis and chills, 8 cases of increased alanine aminotransferase and increased blood creatinine, 7 cases of peripheral sensory neuropathy, 6 cases of fatigue and infusion-related reactions, and 5 cases each of hypokalemia, insomnia, dysgeusia, and palmar-plantar erythrodysesthesia syndrome. A total of 27 unknown adverse reactions occurred in 23 patients, including 2 cases of increased blood creatine phosphokinase, and 1 case each of tumor perforation, disseminated intravascular coagulation, iron deficiency anemia, hyperglycemia, hypoglycemia, hypomagnesemia, vitamin B12 deficiency, dyslipidemia, keratitis, myocardial infarction, arterial thrombosis, subclavian vein thrombosis, embolism, venous thrombosis of the extremities, pneumothorax, pulmonary artery thrombosis, ascites, esophagitis, intestinal volvulus, cholangitis, veno-occlusive liver disease, asteatosis, hematuria, increased amylase, and decreased blood zinc. Twenty serious adverse reactions occurred in 15 patients, including two cases of interstitial lung disease, bacteremia, vascular device infection, tumor perforation, disseminated intravascular coagulation, hyperglycemia, cerebellar hemorrhage, myocardial infarction, cardiac disorder, subclavian vein thrombosis, diarrhea, intestinal volvulus, cholangitis, veno-occlusive liver disease, chest pain, fatigue, pyrexia, increased aspartate aminotransferase, and increased gamma-glutamyltransferase.The outcomes of these side effects were death for myocardial infarction, unknown for cerebellar hemorrhage, no recovery for hyperglycemia, cardiac damage, veno-occlusive liver disease, chest pain, increased aspartate aminotransferase, and increased gamma-glutamyltransferase, and the outcomes of other serious side effects were recovery or improvement. An investigation into factors affecting the occurrence of side effects revealed that the incidence of side effects was significantly higher in patients with "concomitant pulmonary dysfunction" and "treatment period of this drug for 7 months (210 days) or longer," and significantly lower in patients with "previous treatment with trastuzumab." This may be due to the fact that patients with pulmonary dysfunction as a comorbidity have a higher risk of developing side effects compared to patients without it, and that the longer the treatment period of this drug, the higher the risk of developing side effects.Furthermore, cases in which trastuzumab preparations were used in previous treatment may have excluded cases in which treatment was discontinued due to side effects, etc., and this was thought to be due to the drug being used in cases in which the drug had a high tolerance for side effects. There was no significant difference in the incidence of side effects depending on whether or not abnormal findings were found in cardiac and pulmonary function tests performed before the start of administration of this drug. It is believed that the benefits of treatment outweighed the risks, and administration of this drug was continued while closely monitoring the patient's condition. Administration to patients with pulmonary dysfunction is described in the precautions for use, so no additional measures are necessary. Adverse reactions that fall under safety considerations occurred in 90 cases. These included hematologic toxicity in 55 cases (32.16%), hepatic failure/liver damage in 25 cases (14.62%), infusion reaction in 21 cases (12.28%), renal damage in 9 cases (5.26%), interstitial lung disease/pulmonary damage in 6 cases (3.51%), cardiac damage in 5 cases (2.92%), and infection in 5 cases each (2.92%). Furthermore, there were no cases of coma, cerebrovascular disease/cerebral edema, or tumor lysis syndrome. With the exception of liver failure and liver damage, none of these incidence rates were significantly higher than those listed in the latest electronic supplement. The reason for the high incidence of liver failure and liver damage in this survey is thought to be the high rate of oxaliplatin used in chemotherapy in combination with this drug. The section on serious adverse reactions in the electronic package insert for oxaliplatin states that liver dysfunction accompanied by elevated AST (38.9%), elevated ALT (32.6%), elevated bilirubin (6.3%), etc. may occur. Based on the above, we believe that there are no particular safety issues associated with administering this drug as long as we continue to raise caution through electronic package inserts, etc.

The best overall evaluation of 124 patients with target lesions was CR in 3 patients, PR in 40 patients, SD in 59 patients, PD in 20 patients, and NE in 2 patients, for a response rate of 35.3% (43/122 patients). After examining factors affecting efficacy, the response rate in patients with "complications of cardiac dysfunction" was significantly lower at 15.4% (2/13) (p=0.026). The reason for the small number of patients and the significantly lower response rate is unknown. Based on these findings, we believe there are no problems with the efficacy of this drug.

Based on the results of this investigation, the incidence of side effects and the occurrence of the risks listed in the safety considerations for this drug appear to have a profile similar to that of the original biopharmaceutical, and no new safety concerns were identified. Furthermore, since no new concerns were identified regarding efficacy, it has been determined that there is no need to take safety measures, such as revising the precautions for use. Going forward, we will continue to collect informatio

May. 12, 2025

May. 12, 2025

https://link.springer.com/article/10.1007/s40487-025-00341-7?utm_source=rct_congratemailt&utm_medium=email&utm_campaign=oa_20250508&utm_content=10.1007%2Fs40487-025-00341-7

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071230094

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1-1, MARUNOUCHI 2-CHOME, CHIYODA-KU, TOKYO 100-0005, JAPAN

tatsuo.haneji@nipponkayaku.co.jp

Haneji Tatsuo

NIPPON KAYAKU CO., LTD.

1-1, MARUNOUCHI 2-CHOME, CHIYODA-KU, TOKYO 100-0005, JAPAN

+81-8070218144

tatsuo.haneji@nipponkayaku.co.jp

Complete

April. 17, 2018

Observational

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

HER2 positive gastric cancer

Not set: The following is set as a precaution when selecting patients.

Both

HER2 positive gastric cancer

Safety: Adverse events
Efficacy: tumor reduction effect, best overall effect

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