Trastuzumab Deruxtecan outperforms trastuzumab emtansine in HER2-positive breast cancer

foreword

Breast cancer (BC) is the most commonly diagnosed and deadly cancer in women worldwide, with approximately 20% of women having human epidermal growth factor receptor 2 (HER2)-positive breast cancer cancer

Trastuzumab Deruxtecan (T-DXd and DS-8201), a novel ADC, is a combination of a HER2-targeting antibody and a DNA topoisomerase I inhibitor, deruxtecan (DXd)

research method

The study is a phase 3, multicenter, open-label, randomized controlled trial

Research result

T-DM1

①T-DXd treatment has an advantage over T-DM1 in terms of progression-free survival

Figure 1 Kaplan-Meier analysis and subgroup analysis for no survival and development

Figure 1A shows Kaplan-Meier estimates of progression-free survival in the intention-to-treat population (all randomly assigned patients); Hazard ratios and 95% confidence intervals (CIs) for progression survival

②At the data cutoff of the interim analysis, the proportion of patients who were alive at 12 months was 94.

Figure 2 Kaplan-Meier estimates of 12-month overall survival for subjects

③ Figure 3 shows the best percent change from baseline in the sum of the largest measurable tumor diameters in patients: 245 of the 261 patients who received T-DXd (Figure 3A) and 263 of the 263 patients with T-DM1.

Figure 3 Antitumor activity of drugs

④ Safety: The median treatment duration was 14.

Research result

Results of the study showed that trastuzumab-deruxtecan treatment resulted in a significant reduction in HER2-positive metastatic breast cancer compared with trastuzumab-emtansine treatment in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane risk of disease progression or death

Analysis conclusion

T-DXd was superior to T-DM1 in reducing the risk of disease progression or death in patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab plus paclitaxel

Literature interpretation

The study proved that the progression-free survival time of T-DXd was significantly longer than that of T-DM1, and after subgroup analysis of disease history, previous treatment, and hormone receptor status, the T-DXd group still showed lower disease progression or death.

original source

Cortés J, Kim SB, Chung WP, et al.

DOI: 10.