Kadcyla

Adjuvant HER2+ Breast Cancer: Single agent for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.
Metastatic HER2+ Breast Cancer: Single agent for treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.

Recommended dose: 3.6 mg/kg IV every 3 weeks (21-day cycle)
First infusion: Over 90 minutes with observation for 90 minutes
Subsequent infusions: Over 30 minutes if prior infusion tolerated, with 30-minute observation
Dose reductions: First: 3.0 mg/kg; Second: 2.4 mg/kg. Discontinue if unable to tolerate 2.4 mg/kg.
Do not substitute with or for trastuzumab or fam-trastuzumab deruxtecan

For injection: 100 mg, 160 mg lyophilized powder in single-dose vial

None listed in the prescribing information.

• Hepatotoxicity: Serious hepatotoxicity including liver failure and death reported. Monitor hepatic function before each dose. Reduce dose or discontinue for elevated transaminases or bilirubin.
• Left Ventricular Dysfunction: Assess LVEF prior to initiation and at regular intervals. Withhold for LVEF <40% or LVEF 40–45% with ≥10% point decline from baseline.
• Pulmonary Toxicity: Cases of ILD/pneumonitis reported, including fatal cases. Permanently discontinue.
• Infusion-Related Reactions: Slow or interrupt infusion for IRR. Permanently discontinue for life-threatening IRR.
• Hemorrhage: Hemorrhagic events, including CNS hemorrhage, reported. Do not treat patients with preexisting thrombocytopenia (≤100,000/mm³).
• Thrombocytopenia: Monitor platelet counts before each dose.
• Neurotoxicity: Peripheral neuropathy reported. Temporarily discontinue for Grade 3/4.
• Embryo-Fetal Toxicity: Can cause fetal harm.

Fatigue (36%), Nausea (40%), Musculoskeletal Pain (36%), Hemorrhage (32%), Thrombocytopenia (31%), Headache (28%), Increased Transaminases (28%), Constipation (27%), Epistaxis (23%), Arthralgia (19%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

CYP3A4 Inhibitors: DM1 (emtansine) is metabolized mainly by CYP3A4. Avoid concurrent strong CYP3A4 inhibitors when possible due to potential for increased DM1 exposure and toxicity.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Ado-trastuzumab emtansine is an antibody-drug conjugate containing the anti-HER2 humanized IgG1 monoclonal antibody trastuzumab covalently linked to the microtubule inhibitory drug DM1 (derivative of maytansine) via a stable thioether linker (MCC). Upon binding to HER2 on tumor cells, the ADC undergoes receptor-mediated internalization and lysosomal degradation, resulting in intracellular release of DM1-containing catabolites that disrupt microtubules and cause cell death. The antibody component retains mechanisms of action of trastuzumab: inhibition of HER2 signaling, Fc-mediated ADCC, and inhibition of HER2 extracellular domain shedding.

Tmax: end of infusion. ADC Half-life: ~4 days. Vd: 3.13 L. Steady state by Cycle 1. DM1 metabolized by CYP3A4/5. Elimination primarily via catabolism. Minimal urinary excretion.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• EMILIA — T-DM1 vs. lapatinib + capecitabine in HER2+ metastatic breast cancer after trastuzumab + taxane. Phase III, n=991.
  🔬 NCT00829166 ↗ 📄 Primary Publication ↗
• KATHERINE — Adjuvant T-DM1 vs. trastuzumab in HER2+ early breast cancer with residual disease after neoadjuvant therapy. Phase III, n=1486.
  🔬 NCT01772472 ↗ 📄 Primary Publication ↗

Kadcyla has FDA-approved indications across the following cancer types covered on CancerDrugEvidence: