More evidence that the drug-antibody conjugate is effective and safe for patients with advanced disease

The recent FDA approval of the drug-antibody conjugate T-DM1 (trastuzumab emtansine, brand name Kadcyla) had been eagerly anticipated. Its arrival brings to the clinic a novel agent capable of delivering a cytotoxic to its target (human epidermal growth factor receptor 2 [HER2]–positive breast cancer) more effectively and with less toxicity than chemotherapy plus trastuzumab or other anti-HER2 agents such as lapatanib (JW Oncol Hematol Oct 23 2012).

Now, industry-supported investigators report the results of a phase II randomized trial of T-DM1 involving 137 patients with HER2-positive, metastatic or recurrent locally advanced breast cancer. The patients were randomly assigned to receive first-line treatment with trastuzumab plus docetaxel (HT) versus T-DM1 until disease progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety.

After a median follow-up of 23 months, median PFS was significantly improved with T-DM1 versus HT (14.2 vs. 9.2 months ; hazard ratio, 0.59; 95% confidence interval, 0.36–0.97; P=0.035); the median duration of follow-ups was approximately 14 months in both arms. The objective response rate was similar in both treatment arms: 64.2% (95% CI, 51.8%–74.8%) with T-DM1 and 58.0% (95% CI, 45.5%–69.2%) with HT. T-DM1 had a much more favorable toxicity profile compared to HT, with fewer grade ≥3 adverse events, serious AEs, and treatment discontinuations. Overall survival was similar between treatment arms.

Citation(s):

Hurvitz SA et al. Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer. J Clin Oncol 2013 Feb 11.