Saturday, October 19, 2013

FROM MEDSCAPE

Important Safety Information  |   Full Prescribing Information
KADCYLA showed treatment benefit in HER2+ metastatic breast cancer (MBC) in overall survival (OS) and progression-free survival (PFS) vs lapatinib + capecitabine1
For more details about these and other EMILIA trial endpoints, visit KADCYLA.com.
Indication
KADCYLA® (ado-trastuzumab emtansine), as a single agent, is indicated for the treatment of patients with HER2-positive (HER2+), metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
  • Received prior therapy for metastatic disease, or
  • Developed disease recurrence during or within six months of completing adjuvant therapy
KADCYLA extended median OS by nearly 6 months1
50% improvement in median PFS for KADCYLA vs lapatinib + capecitabine1
  • 9.6 months vs 6.4 months; HR=0.650; 95% CI: 0.549, 0.771; P<0.0001
Important Safety Information
Boxed WARNINGS: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY
  • Do Not Substitute KADCYLA for or with Trastuzumab
  • Hepatotoxicity: Serious hepatotoxicity has been reported, including liver failure and death in patients treated with KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases or total bilirubin
  • Cardiac Toxicity: KADCYLA administration may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during treatment with KADCYLA. Withhold treatment for clinically significant decrease in left ventricular function
  • Embryo-Fetal Toxicity: Exposure to KADCYLA can result in embryo-fetal death or birth defects. Advise patients of these risks and the need for effective contraception
Additional Important Safety Information
Left Ventricular Dysfunction (LVD)
  • Patients treated with KADCYLA are at increased risk of developing LVD. In EMILIA, LVD occurred in 1.8% of patients in the KADCYLA-treated group and in 3.3% in the comparator group. Permanently discontinue KADCYLA if LVEF has not improved or has declined further
Pregnancy Registry
  • Advise patients to contact their healthcare provider immediately if they suspect they may be pregnant. Encourage women who may be exposed to KADCYLA during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720
Pulmonary Toxicity
  • Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome have been reported in clinical trials with KADCYLA. In EMILIA, the overall frequency of pneumonitis was 1.2%
  • Treatment with KADCYLA should be permanently discontinued in patients diagnosed with ILD or pneumonitis
Infusion-Related Reactions, Hypersensitivity Reactions
  • Treatment with KADCYLA has not been studied in patients who had trastuzumab permanently discontinued due to infusion-related reactions (IRR) and/or hypersensitivity reactions; treatment with KADCYLA is not recommended for these patients. In EMILIA, the overall frequency of IRRs in patients treated with KADCYLA was 1.4%
  • KADCYLA treatment should be interrupted in patients with severe IRR and permanently discontinued in the event of a life-threatening IRR. Patients should be closely monitored for IRR reactions, especially during the first infusion
Thrombocytopenia
  • In EMILIA, the incidence of ≥ Grade 3 thrombocytopenia was 14.5% in the KADCYLA-treated group and 0.4% in the comparator group (overall incidence 31.2% and 3.3%, respectively)
  • Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose. Institute dose modifications as appropriate
Neurotoxicity
  • In EMILIA, the incidence of ≥ Grade 3 peripheral neuropathy was 2.2% in the KADCYLA-treated group and 0.2% in the comparator group (overall incidence 21.2% and 13.5%, respectively)
  • Monitor for signs or symptoms of neurotoxicity. KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to ≤ Grade 2
HER2 Testing
  • Detection of HER2 protein overexpression or gene amplification is necessary for selection of patients appropriate for KADCYLA. Perform using FDA approved tests by laboratories with demonstrated proficiency
Extravasation
  • In KADCYLA clinical studies, reactions secondary to extravasation have been observed and were generally mild. The infusion site should be closely monitored for possible subcutaneous infiltration during drug administration. Specific treatment for KADCYLA extravasation is unknown
Nursing Mothers
  • Discontinue nursing or discontinue KADCYLA taking into consideration the importance of the drug to the mother
Adverse Reactions
  • The most common ADRs seen with KADCYLA in EMILIA (frequency > 25%) were nausea, fatigue, musculoskeletal pain, thrombocytopenia, increased transaminases, headache, and constipation. The most common NCI-CTCAE (version 3) ≥ Grade 3 ADRs (frequency >2%) were thrombocytopenia, increased transaminases, anemia, hypokalemia, peripheral neuropathy and fatigue
You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Click here for full Prescribing Information for additional important safety information, including Boxed WARNINGS.
Reference: 1. KADCYLA Prescribing Information. Genentech, Inc. May 2013.
© 2013 Genentech USA, Inc. All rights reserved. TDM0001957100
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