Indications for KADCYLA:
As single agent for treatment in patients with HER2-positive (+), 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 6 months of completing adjuvant therapy. Adjuvant treatment in patients with HER2 (+) early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.
Give by IV infusion only over 90mins. 3.6mg/kg max every 3 weeks (21-day cycle). MBC: treat until disease progression or unacceptable toxicity. EBC: treat for a total of 14 cycles unless disease recurrence or unacceptable toxicity. Subsequent infusions may be given over 30mins if previously tolerated. Monitor closely for possible SC infiltration during infusion. Dose modifications: see full labeling.
Hepatotoxicity. Cardiac toxicity. Embryo-fetal toxicity.
Do not substitute for or with trastuzumab. Hepatotoxicity; monitor serum transaminases and bilirubin prior to starting and to each dose; reduce dose or discontinue if occurs. Permanently discontinue if serum transaminases >3×ULN and with total bilirubin >2×ULN, or if nodular regenerative hyperplasia develops. Risk of left ventricular dysfunction. Assess LVEF prior to initiation and every 3 months during treatment; interrupt and discontinue as appropriate. Permanently discontinue if interstitial lung disease or pneumonitis occurs. Adjuvant therapy: permanently discontinue if Grade ≥3 or unresponsive Grade 2 radiation pneumonitis occurs. Monitor for extravasation, infusion-related or hypersensitivity reactions; if significant, slow or interrupt infusion; discontinue if life-threatening. Patients who permanently discontinued trastuzumab due to infusion-related reactions and/or hypersensitivity: not recommended. Monitor platelets at baseline and prior to each dose; if platelets <50,000/mm3, delay dose until recovery to ≥75,000/mm3; if platelets <25,000/mm3, delay until recovery to ≥75,000/mm3 and reduce dose. If thrombocytopenia occurs <100,000/mm3 and concomitant anticoagulants, monitor closely. Monitor for neurotoxicity; withhold temporarily if Grade 3 or 4 peripheral neuropathy occurs. Test for HER2 protein overexpression or gene amplification using FDA-approved tests by labs with demonstrated proficiency. Hepatic impairment: monitor closely. Embryo-fetal toxicity. Advise to use effective contraception during therapy and for 7 months (females) or 4 months (males w. female partners) after last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 7 months after last dose).
HER2-targeted antibody-drug conjugate.
Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, indinavir, ritonavir, nefazodone, nelfinavir, saquinavir, telithromycin); if unavoidable, consider delaying therapy. Caution with concomitant anticoagulation or antiplatelet therapy; monitor closely.
Fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased transaminases, constipation, epistaxis, peripheral neuropathy, arthralgia, oligohydramnios (do fetal testing if occurs), possible infertility.
Report Kadcyla exposure in pregnant women to the pregnancy pharmacovigilance program at (888) 835-2555.