Comment
In 1987, overexpression of the growth-factor receptor HER2 was identified as a negative predictor of outcome in breast cancer patients.1 The protein turned out to be a druggable target, and the creation of trastuzumab—a humanised monoclonal antibody targeting the extracellular domain of HER2—not only revolutionised the treatment in this disease subset, but also marked the advent of targeted therapy in breast oncology. In combination with chemotherapy, trastuzumab yielded significant, clinically relevant prolongation of progression-free and overall survival.2 Although this advance was a major leap forward, disease progression within 18 months is still highly likely, even in primary trastuzumab responders.3 Therefore, new treatment strategies in patients with disease progression on trastuzumab were still needed; established options included the administration of trastuzumab beyond progression,4 the switch to lapatinib plus capecitabine,5 or dual HER2 inhibition with a combination of trastuzumab and lapatinib.6 Trastuzumab emtansine is an antibody–drug conjugate of trastuzumab and the cytotoxic emtansine covalently linked to the antibody by a thiol linker. This first-inclass drug was developed in an attempt to overcome trastuzumab resistance.7 Binding of trastuzumab emtansine to HER2 results in internalisation of the antigen–antibody complex, leading to degradation of trastuzumab and the intracellular release of emtansine. Trastuzumab emtansine is already approved in patients pretreated with taxanes plus trastuzumab because it improved progression-free and overall survival when compared with lapatinib plus capecitabine in the phase 3 EMILIA trial;8 however, no direct comparison of trastuzumab emtansine with trastuzumab beyond progression was done. In The Lancet Oncology, Ian E Krop and colleagues report the results of the TH3RESA trial,9 a randomised phase 3 study comparing trastuzumab emtansine to treatment of physicians’ choice in heavily pretreated (two or more lines) patients with HER2-positive metastatic breast cancer. Median progression-free survival in the trastuzumab emtansine group was nearly double that of patients in the control group (6·2 months vs 3·3 months; HR 0·53 [95% CI 0·42–0·66]; p
In 1987, overexpression of the growth-factor receptor HER2 was identified as a negative predictor of outcome in breast cancer patients.1 The protein turned out to be a druggable target, and the creation of trastuzumab—a humanised monoclonal antibody targeting the extracellular domain of HER2—not only revolutionised the treatment in this disease subset, but also marked the advent of targeted therapy in breast oncology. In combination with chemotherapy, trastuzumab yielded significant, clinically relevant prolongation of progression-free and overall survival.2 Although this advance was a major leap forward, disease progression within 18 months is still highly likely, even in primary trastuzumab responders.3 Therefore, new treatment strategies in patients with disease progression on trastuzumab were still needed; established options included the administration of trastuzumab beyond progression,4 the switch to lapatinib plus capecitabine,5 or dual HER2 inhibition with a combination of trastuzumab and lapatinib.6 Trastuzumab emtansine is an antibody–drug conjugate of trastuzumab and the cytotoxic emtansine covalently linked to the antibody by a thiol linker. This first-inclass drug was developed in an attempt to overcome trastuzumab resistance.7 Binding of trastuzumab emtansine to HER2 results in internalisation of the antigen–antibody complex, leading to degradation of trastuzumab and the intracellular release of emtansine. Trastuzumab emtansine is already approved in patients pretreated with taxanes plus trastuzumab because it improved progression-free and overall survival when compared with lapatinib plus capecitabine in the phase 3 EMILIA trial;8 however, no direct comparison of trastuzumab emtansine with trastuzumab beyond progression was done. In The Lancet Oncology, Ian E Krop and colleagues report the results of the TH3RESA trial,9 a randomised phase 3 study comparing trastuzumab emtansine to treatment of physicians’ choice in heavily pretreated (two or more lines) patients with HER2-positive metastatic breast cancer. Median progression-free survival in the trastuzumab emtansine group was nearly double that of patients in the control group (6·2 months vs 3·3 months; HR 0·53 [95% CI 0·42–0·66]; p
