Disitamab vedotin for HER2-positive breast cancer with liver metastases: phase 3 results from the RC48-C006 phase 2/3 trial

Abstract

Patients with HER2-positive advanced breast cancer with liver metastases (BCLM) have poor prognosis. Study RC48-C006 is a prospective, open-label, multi-center, randomized phase 2/3 trial (ClinicalTrials.gov identifier, NCT03500380). Based on the phase 2 results, the phase 3 stage was initiated to evaluate disitamab vedotin (DV) versus lapatinib plus capecitabine (L + C) in patients with HER2-positive BCLM who were previously treated with trastuzumab and taxanes. The results from the phase 3 stage are reported in this article. A total of 104 patients were randomized at 1:1 to receive DV (53 patients) or L + C (51 patients). Progression-free survival (PFS) assessed by the blinded Independent Review Committee (BIRC) was significantly improved with DV versus with L + C (median: 9.9 vs 4.9 months; stratified hazard ratio [HR]: 0.56 [95.48% CI, 0.35–0.91]; 2-sided P = 0.01), meeting the pre-specified primary endpoint. The investigator-assessed PFS was consistent with the BIRC assessment. Prespecified subgroup analysis of PFS consistently favored DV. Similar incidences of grade ≥3 treatment-related adverse events were reported with DV versus L + C (37.7% vs 36.0%). The present findings support DV as a treatment option for HER2-positive BCLM following trastuzumab and taxane therapy. Patients with HER2-positive breast cancer with liver metastases (BCLM) have poor prognosis. Here, the authors report phase 3 results from the phase 2/3 RC48-C006 clinical trial comparing disitamab vedotin (HER2 targeted antibody drug conjugate) against lapatinib plus capecitabine in patients with HER2-postivie breast cancer with liver metastases previously treated with trastuzumab and taxanes.