The FDA has now approved ado-trastuzumab emtansine (Kadcyla®, Genentech Inc) for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease following neoadjuvant taxane and trastuzumab-based treatment.
The clinical trial KATHERINE (NCT01772472), results of which were published in The New England Journal of Medicine, contained a population of 1,486 patients with HER2-positive early breast cancer. In order to qualify for the study, patients needed breast tumor tissue samples that revealed HER2 overexpression, defined as 3+ IHC or ISH amplification ration ≥2.0 as determined using an FDA-approved companion diagnostic. In addition, patients had to have residual invasive tumor in the breast and/or axillary lymph nodes following neoadjuvant taxane and trastuzumab-based therapy.
Patients were assigned in a 1:1 ratio to receive either 3.6 mg/kg intravenous ado-trastuzumab emtansine or 6 mg/kg intravenous trastuzumab on day 1 of a 21-day cycle for 14 cycles. Patients received radiotherapy and/or hormonal therapy concurrent with study treatment per local guidelines. When the researchers followed up with the patients after a median of 40 months, they found that invasive disease or death occurred in 91 patients in the ado-trastuzumab emtansine group compared with 165 patients in the trastuzumab (12.2% vs 22.2%).
The most common treatment-related adverse events, occurring in at least 25% of patients, included fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia.
"Approval of [ado-trastuzumab emtansine] by the FDA following their extensive review of the KATHERINE efficacy and safety data is very gratifying on two levels. Of most importance, it is essential for making the therapy available for higher risk patients who can benefit from [ado-trastuzumab emtansine] ," commented one of the study authors, Charles Geyer, MD, Professor of Internal Medicine at Virginia Commonwealth University. "Approval also reflects validation of a novel approach of conducting a potential indication study of a promising new therapy such as [ado-trastuzumab emtansine] in a high-risk group identified by failure of standard neoadjuvant therapies to eliminate their breast cancers prior to surgery."
For More Information
Clinicaltrials.gov (2019). A study of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor in the breast or axillary lymph nodes following preoperative therapy (KATHERINE). NLM identifier: NCT01772472.
Von Minckwitz G, Huang CS, Mano MS, et al (2019). Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med, 380(7):617-628. DOI:10.1056/NEJMoal1814017
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