T dm1 clinical trials plus#
Results showed a clear advantage for T-DM1 over capecitabine plus lapatinib in PFS (9.6 vs 6.4 months hazard ratio, 0.65 p < 0.001) and overall survival (OS) (30.9 vs 25.1 months HR, 0.68 p < 0.001). Patients were randomized to receive T-DM1 (3.6 mg/kg every 21 days) or capecitabine plus lapatinib.
T dm1 clinical trials trial#
The randomized phase III EMILIA trial included 991 HER2-positive metastatic or locally advanced breast cancer patients who had previously received trastuzumab and a taxane. Finally, emtansine is released into the cytoplasm, where it acts to disrupt microtubules and inhibit HER2 signaling, resulting in cell-cycle arrest and apoptosis 11, 12. In T-DM1, trastuzumab and emtansine are linked by a stable thioether linker that stabilizes the conjugate until it reaches the target HER2 receptor, where it undergoes receptor-mediated internalization and subsequent lysosomal degradation. In vitro studies have shown that emtansine is 40 times more powerful than taxanes, maintaining efficacy without increasing toxicity. Emtansine is an antimicrotubule that inhibits tubulin polymerization. Trastuzumab is a humanized monoclonal antibody that binds selectively to the HER2 membrane receptor, inducing apoptosis and activating cell immunity. T-DM1 is an antibody drug conjugate that combines the action of trastuzumab with that of emtansine. Recent data from KATHERINE trial, among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, has shown a reduction of 50% of the risk of recurrence of invasive breast cancer or death with adjuvant T-DM1 instead of trastuzumab alone 10. Several studies have shown that the combination of trastuzumab plus emtansine (T-DM1) is active in HER2-positive breast cancer patients who have progressed after prior treatment 6, 7, 8, 9. However, patients will eventually relapse and require a second line of treatment. The combination of trastuzumab, pertuzumab, and a taxane significantly prolonged progression-free survival (PFS) in a randomized trial 5 and is now the standard first-line treatment for HER2-positive breast cancer. Treatment of patients with HER2-positive breast cancer has evolved rapidly since the identification of HER2 as an ideal target for anticancer agents. HER2 is amplified in about 20% of invasive breast cancers and is associated with a more aggressive disease and poor clinical outcome 3, 4. Over the last ten years, a new molecular classification of breast cancer has been developed that includes the human epidermal growth receptor 2 (HER2), a member of the ErbB family. Our real-world data thus confirm and support the findings of the two major phase III trials and indicate the usefulness of T-DM1 in routine clinical practice.īreast cancer is the most common malignancy in women worldwide and is the cause of more than 570,000 deaths every year 1, 2.
T dm1 clinical trials series#
In our series of patients, T-DM1 has demonstrated efficacy in the treatment of HER2-positive metastatic breast cancer.
Our findings are in line with those of the EMILIA study and slightly superior to those of the TH3RESA study. Among five patients with metastases of the central nervous system, PFS was six months, OS was not reached, and the objective response rate was 80%. PFS was ≥12 months in five patients, three of whom attained a PFS of ≥23 months. Progression-free survival (PFS) was 10 months compared with the 9.6 months of the EMILIA trial and the 6.2 months of the TH3RESA trial, overall survival was 34 months compared with the 29.9 months of the EMILIA trial and the 22.7 months of the TH3RESA trial. We have retrospectively analyzed outcomes in these patients and compared our findings with those of the two clinical trials. From 2012 to 2016, 15 patients with HER2-positive breast cancer who had progressed to prior treatment received T-DM1 at our center. We have performed a real-world study to complement the findings of the clinical trials. In two phase III clinical trials, EMILIA and TH3RESA, T-DM1 was shown to be effective in HER2-positive metastatic breast cancer patients who had progressed to taxanes and trastuzumab. T-DM1 is an antibody drug conjugate that combines trastuzumab with emtansine via a stable thioether linker.
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