Trastuzumab deruxtecan significantly improves PFS in certain breast cancer patients

The antibody-drug conjugate trastuzumab deruxtecan delays cancer growth for women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer that has progressed following endocrine therapy, according to findings from a new phase 3 clinical trial. The data was presented at the 2024 ASCO Annual Meeting.

This study included 866 participants with metastatic breast cancer that was either HER2-low (713 participants) or HER2-ultralow (153 participants). All study participants had received at least one treatment with endocrine therapy, and nearly all participants (90.4 per cent) had also received targeted therapy with a CDK4/6 inhibitor. The participants were randomly assigned to receive either trastuzumab deruxtecan (436 participants) or a chemotherapy of their doctor’s choice (430 participants, who received either capecitabine, nab-paclitaxel, or paclitaxel).

For those with HER2-low cancer, the PFS was 13.2 months for those who received trastuzumab deruxtecan vs 8.1 months for those who received chemotherapy. Similar results were seen in the small group of patients with HER2-ultralow cancer.

Overall, the patients with HER2-low cancer who received trastuzumab deruxtecan had a 38 per cent lower chance of their cancer growing or spreading compared to those who received chemotherapy.

For those with HER2-low cancer, the objective response rate (ORR) was 56.5 per cent for those who received trastuzumab deruxtecan vs 32.3 per cent for those who received chemotherapy.

For those with HER2-ultralow cancer, the ORR more than doubled for those who received trastuzumab deruxtecan compared with those who received chemotherapy (61.8 vs 26.3 per cent, respectively).

Participants who received trastuzumab deruxtecan were able to receive their treatment for a longer time without experiencing severe side-effects, with a median treatment length of 11 vs 5.6 months for those who received chemotherapy. 

Serious side-effects were more common in the trastuzumab deruxtecan group, with about 41 per cent of participants experiencing a serious side-effect vs about 31 per cent of those who received chemotherapy.

“These results also represent a potential shift in how we classify and treat metastatic breast cancer, as we may have the opportunity to use trastuzumab deruxtecan earlier in the treatment of HR+ metastatic breast cancer and expand trastuzumab deruxtecan into new metastatic breast cancer patients who previously have not been able to benefit from a targeted medicine post-endocrine therapy,” said Dr Giuseppe Curigliano, European Institute of Oncology, Milan, Italy.

The researchers are planning to continue following the patients to assess overall survival outcomes.