Unresectable or Metastatic HER2-Mutant NSCLC (5.4 mg/kg)ĭESTINY-Lung02 evaluated two dose levels (5.4 mg/kg and 6.4 mg/kg ) however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (71%), decreased hemoglobin (66%), decreased neutrophil count (65%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (47%), increased aspartate aminotransferase (48%), vomiting (44%), increased alanine aminotransferase (42%), alopecia (39%), increased blood alkaline phosphatase (39%), constipation (34%), musculoskeletal pain (32%), decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and respiratory infection (24%). Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF 6 months and 39% were exposed for >1 year. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. If LVEF of 20% is confirmed, permanently discontinue ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is 20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. Manage LVEF decrease through treatment interruption. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Febrile neutropenia was reported in 1.1% of patients. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664). Sixteen percent had Grade 3 or 4 decreased neutrophil count. In patients with HER2-mutant NSCLC and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. For Grade 3 neutropenia (Absolute Neutrophil Count 38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated.
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23).
Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. In patients with HER2-mutant NSCLC and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. HER2-Mutant NSCLC and Other Solid Tumors (5.4 mg/kg) Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (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. For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). If resolved in >28 days from date of onset, reduce dose one level. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. Consider consultation with a pulmonologist. Evaluate patients with suspected ILD by radiographic imaging. Monitor patients for signs and symptoms of ILD. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients of these risks and the need for effective contraception. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm.Advise patients of the risk and to immediately report symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms.
Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU.WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
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