KADCYLA

What it is

Kadcyla contains trastuzumab emtansine. It is supplied as a powder for concentrate for solution for infusion. Kadcyla is available as a single-use vial containing 100 mg or 160 mg of trastuzumab emtansine. Trastuzumab emtansine is a HER2-targeted antibody-drug conjugate, containing the humanised anti-HER2 IgG1 antibody trastuzumab, covalently linked to the small molecule cytotoxin, DM1.

Approved indications

— Adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. — Treatment of patients with HER2-positive metastatic (Stage IV) breast cancer who previously received trastuzumab and a taxane, separately or in combination, and have either received prior therapy for metastatic disease or developed disease recurrence during or within six months of completing adjuvant therapy.

Dosing overview

The recommended dose of Kadcyla is 3.6 mg/kg, administered as an intravenous infusion every 3 weeks (21-day cycle). Patients with early breast cancer should receive treatment for a total of 14 cycles unless there is disease recurrence or unmanageable toxicity. Patients with metastatic breast cancer should receive treatment until disease progression or unmanageable toxicity.

Key safety warnings

Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or a fatal outcome, have been reported in clinical trials with Kadcyla. Signs and symptoms include dyspnoea, cough, fatigue, and pulmonary infiltrates. It is recommended that treatment with Kadcyla be permanently discontinued in patients who are diagnosed with ILD or pneumonitis, except for radiation pneumonitis in the adjuvant setting, where Kadcyla should be permanently discontinued for Grade 3 or greater or for Grade 2 not responding to standard treatment. 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 the dose or discontinue Kadcyla as appropriate in cases of increased serum transaminases and/or total bilirubin. Serious hepatobiliary disorders, including nodular regenerative hyperplasia (NRH) of the liver and some with a fatal outcome due to drug-induced liver injury have been observed in patients treated with Kadcyla in clinical trials. Kadcyla may lead to reductions in left ventricular ejection fraction (LVEF). LVEF less than 40% has been observed in patients treated with Kadcyla. Symptomatic congestive heart failure (CHF) is a potential risk. Assess LVEF (echocardiogram or multigated acquisition scanning) prior to initiation and at regular intervals (for example, every three months) during treatment with Kadcyla to ensure LVEF is within the institution's normal limits. Thrombocytopenia, or decreased platelet counts, was reported in patients in clinical trials of Kadcyla. The majority of these patients had Grade 1 or 2 events (greater than or equal to 50,000/mm³), with the nadir occurring by day 8 and generally improving to grade 0 or 1 (greater than or equal to 75,000/mm³) by the next scheduled dose. It is recommended that platelet counts are monitored prior to each Kadcyla dose. Cases of haemorrhagic events, including central nervous system, respiratory, and gastrointestinal haemorrhage, have been reported with Kadcyla treatment. Some of these bleeding events resulted in fatal outcomes. In some of the observed cases the patients had thrombocytopenia, or were also receiving anti-coagulation therapy or antiplatelet therapy. Peripheral neuropathy, mainly Grade 1 and predominantly sensory, has been reported in clinical trials of Kadcyla. Treatment with Kadcyla should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until symptoms resolve or improve to Grade 2 or less.

Contraindications

Kadcyla is contraindicated in patients with a known hypersensitivity to Kadcyla or any of its excipients.

PBS listing

Kadcyla powder for intravenous infusion 100 mg is listed on the PBS with authority required restriction and an ex-manufacturer price of A$1482.83.

Regulatory history

Kadcyla trastuzumab emtansine 100 mg and 160 mg powder for injection vials were first listed on the ARTG on 3 September 2013. An AusPAR was issued on 26 August 2013. Kadcyla was approved by the TGA for the treatment of HER2 positive metastatic breast cancer. In November 2014, the PBAC recommended Kadcyla for the treatment of HER2-positive metastatic breast cancer in patients who have received prior trastuzumab and a taxane. In November 2019, the PBAC recommended a change to allow Kadcyla for adjuvant treatment of HER2-positive early breast cancer with residual disease following neoadjuvant HER2-targeted therapy, noting high clinical need, significant improvement in invasive disease-free survival, and acceptable cost-effectiveness.