Enhertu

HOS-099207 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile Enhertu as monotherapy Enhertu 5.4 mg/kg The pooled safety population has been evaluated for patients who received at least one dose of Enhertu 5.4 mg/kg (n = 3057) across multiple tumour types in clinical studies. The median duration of treatment in this pool was 9.9 months (range: 0.2 to 76.0 months). The most common adverse reactions were nausea (70.3%), fatigue (56.9%), vomiting (36.5%), neutropenia (35.9%), anaemia (35.4%), alopecia (34.4%), constipation (33.0%), diarrhoea (30.3%), decreased appetite (29.3%), transaminases increased (27.2%), musculoskeletal pain (24.0%), thrombocytopenia (23.4%) and leukopenia (20.8%). The most common National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE v.5.0) Grade 3 or 4 adverse reactions were neutropenia (18.5%), anaemia (9.9%), fatigue (8.2%), leukopenia (5.8%), thrombocytopenia (5.2%), nausea (4.8%), lymphopenia (4.2%), transaminases increased (3.7%), hypokalaemia (3.6%), diarrhoea (2.5%), vomiting (2.4%), decreased appetite (1.6%), pneumonia (1.4%) and ejection fraction decreased (1.0%). Grade 5 adverse reactions occurred in 1.1% of patients, including ILD/pneumonitis (1.0%). Dose interruptions due to adverse reactions occurred in 34.3% of patients treated with Enhertu. The most frequent adverse reactions associated with dose interruption were neutropenia (12.7%), fatigue (4.4%), anaemia (4.3%), upper respiratory tract infection (3.8%), leukopenia (3.1%), ILD/pneumonitis (3.0%), thrombocytopenia (2.8%) and pneumonia (2.5%). Dose reductions occurred in 21.1% of patients treated with Enhertu. The most frequent adverse reactions associated with dose reduction were 9 fatigue (5.9%), nausea (4.9%), neutropenia (3.3%) and thrombocytopenia (2.2%). Discontinuation of therapy due to an adverse reaction occurred in 10.8% of patients treated with Enhertu. The most frequent adverse reaction associated with permanent discontinuation was ILD/pneumonitis (8.7%). Enhertu 6.4 mg/kg The pooled safety population has been evaluated for patients who received at least one dose of Enhertu 6.4 mg/kg (n = 1133), across multiple tumour types in clinical studies. The median duration of treatment in this pool was 5.1 months (range: 0.4 to 41.0 months). The most common adverse reactions were nausea (64.3%), fatigue (57.3%), anaemia (47.9%), decreased appetite (46.8%), neutropenia (45.9%), vomiting (34.7%), diarrhoea (33.

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HOS-099203 · has-contraindication-information · PDF-Seite 7

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-099202 · has-indication-information · PDF-Seite 2

Breast cancer HER2-positive breast cancer Enhertu in combination with pertuzumab is indicated for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer (for biomarker-based patient selection, see section 4.2). Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens. HER2-low and HER2-ultralow breast cancer Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic • hormone receptor (HR)-positive, HER2-low or HER2-ultralow breast cancer who have received at least one endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment (see sections 4.2 and 5.1). 2  • HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy (see section 4.2). Non-small cell lung cancer (NSCLC) Enhertu as monotherapy is indicated for the treatment of adult patients with advanced NSCLC whose tumours have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy. Gastric cancer Enhertu as monotherapy is indicated for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab- based regimen. Other unresectable or metastatic solid tumours Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumours who have received prior treatment and who have no satisfactory treatment options (see sections 4.4 and 5.1; for biomarker-based patient selection, see section 4.2).

HOS-099205 · has-interaction-information · PDF-Seite 8

Co-administration with ritonavir, an inhibitor of OATP1B, CYP3A and P-gp, or with itraconazole, a strong inhibitor of CYP3A and P-gp, resulted in no clinically meaningful (approximately 10-20%) increase in exposures of trastuzumab deruxtecan or the released topoisomerase I inhibitor, DXd. No dose adjustment is required during co-administration of trastuzumab deruxtecan with medicinal products that are inhibitors of CYP3A or OATP1B or P-gp transporters (see section 5.2).

HOS-099206 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception in males and females Pregnancy status of women of childbearing potential should be verified prior to initiation of Enhertu. Women of childbearing potential should use effective contraception during treatment with Enhertu and for at least 7 months following the last dose. Men with female partners of childbearing potential should use effective contraception during treatment with Enhertu and for at least 4 months following the last dose. Pregnancy There is no available data on the use of Enhertu 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 Enhertu, DXd, can be expected to cause embryo-foetal harm when administered to a pregnant woman (see section 5.3). 8 Administration of Enhertu 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 Enhertu or within 7 months following the last dose of Enhertu, close monitoring is recommended. Breast-feeding 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 Enhertu 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 Enhertu for the mother. Fertility No dedicated fertility studies have been conducted with trastuzumab deruxtecan. Based on results from animal toxicity studies, Enhertu 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 t

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HOS-099204 · has-warning-information · PDF-Seite 7

In order to prevent medicinal product errors, it is important to check the vial labels to ensure that the medicinal product being prepared and administered is Enhertu (trastuzumab deruxtecan) and not trastuzumab or trastuzumab emtansine. Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Interstitial lung disease/pneumonitis Cases of interstitial lung disease (ILD), and/or pneumonitis, have been reported with Enhertu or Enhertu in combination with pertuzumab (see section 4.8). Fatal outcomes have been observed. Patients should be advised to immediately report cough, dyspnoea, fever and/or any new or worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD/pneumonitis. Evidence of ILD/pneumonitis should be promptly investigated. Patients with suspected ILD/pneumonitis should be evaluated by radiographic imaging, preferably a computed tomography (CT) scan. Consultation with a pulmonologist should be considered. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥ 0.5 mg/kg/day prednisolone or equivalent). Enhertu should be withheld until recovery to Grade 0 and may be resumed according to instructions in Table 2 (see section 4.2). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate corticosteroid treatment (e.g., ≥ 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Enhertu should be permanently discontinued in patients who are diagnosed with symptomatic (Grade 2 or greater) ILD/pneumonitis (see section 4.2). Patients with a history of ILD/pneumonitis or patients with moderate or severe renal impairment may be at increased risk of developing ILD/pneumonitis and should be monitored carefully (see section 4.2). Fatal cases of pneumonia, including two cases adjudicated as ILD, were observed. Neutropenia Cases of neutropenia, including febrile neutropenia with a fatal outcome, were reported in clinical studies of Enhertu or Enhertu in combination with pertuzumab. Complete blood counts should be monitored prior to initiation of Enhertu and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, Enhertu may require dose interruption or reduction (see section 4.2). Left ventricular dysfunction Left ventricular dysfunction (LVD) has been observed with anti

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