On the 3rd of May 2019, the FDA approved ado-trastuzumab emtansine (Kadcyla® [T-DM1], Genentech/Roche) as adjuvant therapy for human epidermal growth factor receptor (HER2)-positive early breast cancer (EBC) patients with residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab.

Patients should be selected for T-DM1 treatment by FDA-approved companion diagnostic (CDx). Concurrent to the expansion of the Kadcyla® label, the FDA approved two CDx for Kadcyla®; 1) the Ventana Medical Systems, Inc. PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay, and 2) the INFORM HER2 Dual ISH DNA Probe Cocktail assay.

KATHERINE study

The FDA approval was based on the randomised, multicentre, open-label KATHERINE trial (NCT01772472) comparing T-DM1 with trastuzumab 1:1 in 1486 HER2-positive (3+ IHC or ISH amplification ratio ≥ 2.0 by CDx) EBC patients who had received prior neoadjuvant treatment with a taxane and trastuzumab after which residual invasive cancer in the breast or axillary lymph nodes. Concurrent to the study treatment, patients received radiotherapy and hormonal therapy as per local guidelines. The primary efficacy endpoint was the invasive disease-free survival (IDFS; the time from randomisation to the first occurrence of ipsilateral invasive breast cancer recurrence, ipsilateral local or regional invasive breast tumour recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause).

At a median follow-up of 40 months, the KATHERINE trial showed a significant improvement in IDFS favouring patients treated with T-DM1 when compared to patients treated with trastuzumab (HR=0.50; 95% CI, 0.39-0.64; P<0.0001). The overall survival data were not yet mature at the time of analysis.

Safety

Common adverse reactions in ≥25% of patients treated with T-DM1 included fatigue, nausea, increased transaminases, musculoskeletal pain, haemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia.

Full prescribing information Kadcyla®.