Trastuzumab deruxtecan interacts in the following cases:
No dedicated fertility studies have been conducted with trastuzumab deruxtecan. Based on results from animal toxicity studies, trastuzumab deruxtecan may impair male reproductive function and fertility. It is not known whether trastuzumab deruxtecan or its metabolites are found in seminal fluid. Before starting treatment, male patients should be advised to seek counselling on sperm storage. Male patients must not freeze or donate sperm throughout the treatment period, and for at least 4 months after the final dose of trastuzumab deruxtecan.
There are no available data on the use of trastuzumab deruxtecan in pregnant women. However, trastuzumab, a HER2 receptor antagonist, can cause foetal harm when administered to a pregnant woman. In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios in some cases manifested as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Based on findings in animals and its mechanism of action, the topoisomerase I inhibitor component of trastuzumab deruxtecan, DXd, can be expected to cause embryo-foetal harm when administered to a pregnant woman.
Administration of trastuzumab deruxtecan to pregnant women is not recommended, and patients should be informed of the potential risks to the foetus before they become pregnant. Women who become pregnant must immediately contact their doctor. If a woman becomes pregnant during treatment with trastuzumab deruxtecan or within 7 months following the last dose of trastuzumab deruxtecan, close monitoring is recommended.
It is not known if trastuzumab deruxtecan is excreted in human milk. Human IgG is secreted in human milk, and the potential for absorption and serious adverse reactions to the infant is unknown. Therefore, women should not breast-feed during treatment with trastuzumab deruxtecan or for 7 months after the last dose. A decision should be made to discontinue breast-feeding or to discontinue treatment taking into account the benefit of breast-feeding for the child and/or benefit of treatment with trastuzumab deruxtecan for the mother.
No dedicated fertility studies have been conducted with trastuzumab deruxtecan. Based on results from animal toxicity studies, trastuzumab deruxtecan may impair male reproductive function and fertility. It is not known whether trastuzumab deruxtecan or its metabolites are found in seminal fluid. Before starting treatment, male patients should be advised to seek counselling on sperm storage. Male patients must not freeze or donate sperm throughout the treatment period, and for at least 4 months after the final dose of trastuzumab deruxtecan.
Pregnancy status of women of childbearing potential should be verified prior to initiation of trastuzumab deruxtecan.
Women of childbearing potential should use effective contraception during treatment with trastuzumab deruxtecan and for at least 7 months following the last dose.
Men with female partners of childbearing potential should use effective contraception during treatment with trastuzumab deruxtecan and for at least 4 months following the last dose.
Trastuzumab deruxtecan may have a minor influence on the ability to drive and use machines. Patients should be advised to use caution when driving or operating machinery in case they experience fatigue, headache or dizziness during treatment with trastuzumab deruxtecan.
The most common adverse reactions were nausea (79.9%), fatigue (60.3%), vomiting (48.7%), alopecia (46.2%), constipation (35.9%), decreased appetite (34.6%), anaemia (33.8%), neutropenia (32.5%), diarrhoea (30.8%), thrombocytopenia (23.1%), cough (21.4%), leukopenia (20.5%), and headache (20.1%).
The most common National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE v.4.03) Grade ≥3 adverse reactions were neutropenia (18.8%), anaemia (9.0%), nausea (6.8%), fatigue (6.4%), leukopenia (5.6%), lymphopenia (5.1%), vomiting (4.3%), thrombocytopenia (4.3%), hypokalaemia (3.4%), interstitial lung disease (ILD, 3.0%), diarrhoea (2.6%), febrile neutropenia (1.7%), dyspnoea (1.7%), abdominal pain (1.3%), decreased appetite (1.3%), and alanine aminotransferase increased (1.3%). In 2.6% of patients, ILD led to death.
Dose interruptions due to adverse reactions occurred in 27% of patients treated with trastuzumab deruxtecan. The most frequent adverse reactions associated with dose interruption were neutropenia (14.5%), anaemia (3.4%), upper respiratory tract infection (3.0%), leukopenia (3.0%), ILD (2.6%), thrombocytopenia (2.6%), and fatigue (2.1%). Dose reductions occurred in 15% of patients treated with trastuzumab deruxtecan. The most frequent adverse reactions associated with dose reduction were fatigue (3.8%), nausea (3.4%), and neutropenia (3.4%). Discontinuation of therapy due to an adverse reaction occurred in 12% of patients treated with trastuzumab deruxtecan. The most frequent adverse reaction associated with permanent discontinuation was ILD (9.4%).
The safety of trastuzumab deruxtecan has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of trastuzumab deruxtecan 5.4 mg/kg in clinical studies. The median duration of exposure to trastuzumab deruxtecan was 9.8 months (range: 0.7 to 37.1 months).
The adverse reactions in patients who received at least one dose of trastuzumab deruxtecan in clinical studies are presented in the following table. The adverse reactions are listed by MedDRA system organ class (SOC) and categories of frequency. Frequency categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Adverse reactions in patients treated with trastuzumab deruxtecan:
| System organ class/preferred term or grouped term | Frequency |
|---|---|
| Infections and infestations | |
| Upper respiratory tract infectiona | Very common |
| Blood and lymphatic system disorders | |
| Neutropeniab | Very common |
| Anaemiac | Very common |
| Leukopeniad | Very common |
| Lymphopeniae | Very common |
| Thrombocytopeniaf | Very common |
| Febrile neutropenia | Common |
| Metabolism and nutrition disorders | |
| Hypokalaemia | Very common |
| Decreased appetite | Very common |
| Nervous system disorders | |
| Headacheg | Very common |
| Dizziness | Very common |
| Eye disorders | |
| Dry eye | Very common |
| Respiratory, thoracic and mediastinal disorders | |
| Interstitial lung diseaseh | Very common |
| Dyspnoea | Very common |
| Cough | Very common |
| Epistaxis | Very common |
| Gastrointestinal disorders | |
| Nausea | Very common |
| Vomiting | Very common |
| Diarrhoea | Very common |
| Abdominal paini | Very common |
| Constipation | Very common |
| Stomatitisj | Very common |
| Dyspepsia | Very common |
| Skin and subcutaneous tissue disorders | |
| Alopecia | Very common |
| Rashk | Very common |
| General disorders and administration site conditions | |
| Fatiguel | Very common |
| Investigations | |
| Alanine aminotransferase increased | Very common |
| Aspartate aminotransferase increased | Very common |
| Ejection fraction decreasedm | Very common |
| Injury, poisoning and procedural complications | |
| Infusion-related reactionsn | Common |
a Includes influenza, influenza-like illness, and upper respiratory tract infection.
b Includes neutropenia and neutrophil count decreased.
c Includes anaemia, haemoglobin decreased, red blood cell count decreased, and haematocrit decreased.
d Includes leukopenia and white blood cell count decreased.
e Includes lymphopenia and lymphocyte count decreased.
f Includes thrombocytopenia and platelet count decreased.
g Includes headache, sinus headache, and migraine.
h Interstitial lung disease includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organising pneumonia, acute respiratory failure, lung infiltration, lymphangitis, and alveolitis.
i Includes abdominal discomfort, gastrointestinal pain, abdominal pain, abdominal pain lower, and abdominal pain upper.
j Includes stomatitis, aphthous ulcer, mouth ulceration, oral mucosa erosion, and oral mucosal blistering.
k Includes rash, rash pustular, and rash maculopapular.
l Includes fatigue and asthenia.
m Includes laboratory parameters of LVEF decrease (n=37) and/or preferred terms of ejection fraction decreased (n=3), cardiac failure (n=1) and cardiac failure congestive (n=1).
n Cases of infusion-related reactions include infusion-related reaction (n=4), hypersensitivity (n=1), and flushing (n=1).
In clinical studies (n=234), ILD occurred in 15.0% of patients. Most ILD cases were Grade 1 (3.0%), Grade 2 (8.5%) or Grade 3 (0.4%). Grade 5 events occurred in 3.0% of patients. Median time to first onset was 5.5 months (range: 1.2 to 20.8).
In clinical studies (n=234), a decrease in neutrophil count was reported in 32.5% of patients and 18.8% had Grade 3 or 4 events. Median time of onset was 53 days (range: 8 days to 18.0 months), and median duration of the first event was 22 days (range: 2 days to 9.0 months). Febrile neutropenia was reported in 1.7% of patients.
As with all therapeutic proteins, there is a potential for immunogenicity. Across all doses evaluated in clinical studies, 0.6% (4/640) of evaluable patients developed antibodies against trastuzumab deruxtecan following treatment with trastuzumab deruxtecan. There was no association between development of antibodies and allergic-type reactions.
Safety has not been established in this population.
Of the 234 patients with HER2-positive breast cancer treated with trastuzumab deruxtecan 5.4 mg/kg, 26% were 65 years or older and 5% were 75 years or older. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged 65 years or older (49%) as compared to younger patients (39%), leading to more discontinuations due to adverse reactions.
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