Real-world data on T-DM1 efficacy – results of a single-center retrospective study of HER2-positive breast cancer patients

Abstract

T-DM1 is an antibody drug conjugate that combines trastuzumab with emtansine via a stable thioether linker. 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. We have performed a real-world study to complement the findings of the 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 retrospectively analyzed outcomes in these patients and compared our findings with those of the two clinical trials. 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. PFS was ≥12 months in five patients, three of whom attained a PFS of ≥23 months. 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%. Our findings are in line with those of the EMILIA study and slightly superior to those of the TH3RESA study. In our series of patients, T-DM1 has demonstrated efficacy in the treatment of HER2-positive metastatic breast cancer. 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.

RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer

“…This is in agreement with several clinical studies demonstrating higher response rates of T-DM1 in patients with HER2 mRNA levels above the median compared to the below-median subgroup 14 , 15 , 20 . Importantly, despite its highly targeted mechanism, T-DM1 shows clinical benefit only in a subset of HER2- positive breast cancer patients with an objective response rate reported to ~40% 8 , 21 , 22 . Furthermore, in HER2-positive gastric cancer, an objective T-DM1 response rate of only ~20% with no increase in efficacy compared to taxanes is reported 23 .…”

The Cellular Prion Protein: A Promising Therapeutic Target for Cancer

“…The drugs bind to the molecular target, causing apoptosis of the tumor cells. A representative example of a successful ADC is Trastuzumab Emtansine (T-DM1) [107][108][109]. T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer who were previously treated with trastuzumab and a taxane.…”

Pyrotinib in the Treatment of Women With HER2-Positive Advanced Breast Cancer: A Multicenter, Prospective, Real-World Study

“…This study was carried out to analyze the efficacy and safety of pyrotinib-based therapy in patients with HER2-positive breast cancer in the real world. The most inspiring result of the study was a mPFS of 12.0 months, higher than that of trastuzumab (10.9 months) and T-DM1 (10.0 months) in the real-world setting (19,20), and close to the mPFS result (12.5 months) of pyrotinib in the phase III PHOEBE study (14). In addition, the ORR of pyrotinib-based therapy in this study was 38.6% was also superior to that of T-DM1 (20.0%) (15).…”

“…Our results also confirmed that pyrotinib-based therapy with capecitabine achieved a numerically higher ORR and longer mPFS than that without capecitabine, which merits further assessment in the future. In addition, among patients with brain metastases, the 6-month and 12-month PFS rates were 70.0% and 60.0%, respectively, numerically better than that of anti-HER2 monoclonal antibodies in patients with brain metastases (19,24,25), indicating that pyrotinib is an important treatment option for patients with brain metastases.…”