FDA Approval: Ado-trastuzumab Emtansine for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer
Cet article présente les données ayant servi de base à l'autorisation de mise sur le marché récemment délivrée par la Food and Drug Administation pour l'ado-trastuzumab emtansine dans le traitement des patientes atteintes d'un cancer métastatique du sein HER2+
On February 22, 2013, the FDA licensed ado-trastuzumab emtansine (Kadcyla, Genentech, Inc.) for use as a single agent for the treatment of patients with HER2-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. The clinical basis for licensure was a phase 3 trial in 991 patients with HER2-positive MBC which randomly allocated patients to receive ado-trastuzumab emtansine (N=495) or lapatinib in combination with capecitabine (N=496). The co-primary endpoints were progression-free survival (PFS) based on tumor assessments by an independent review committee and overall survival (OS). Statistically significant improvements in PFS and OS were observed in patients receiving ado-trastuzumab emtansine compared to patients receiving lapatinib plus capecitabine [difference in PFS medians of 3.2 months, HR 0.65 (95% CI, 0.55-0.77), p < 0.0001 and difference in OS medians of 5.8 months, HR 0.68 (95% CI, 0.55- 0.85), p = 0.0006]. The most common adverse reactions in patients receiving ado-trastuzumab emtansine were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased transaminases, and constipation. Other significant adverse reactions included hepatobiliary disorders and left ventricular dysfunction. Given the PFS and OS results, the benefit-risk profile was considered favorable.