Data from a Phase III study of Disitamab Vedotin (DV) in treating patients with HER2-positive advanced breast cancer with liver metastasis (BCLM) were presented at the 47th San Antonio Breast Cancer Symposium (SABCS). The study (RC48-C006, NCT03500380), sponsored by RemeGen Co. Ltd., is the first prospective, randomized Phase III trial globally to demonstrate significant efficacy of a HER2-targeting antibody-drug conjugate (ADC) in this challenging patient population.
Professor Jiayu Wang from the Cancer Hospital, Chinese Academy of Medical Sciences, presented the findings, highlighting the unmet need for effective therapies in this subset of patients, who typically have a poor prognosis with a 5-year survival rate of only 8% to 12%. Approximately 45% of patients with HER2-positive advanced breast cancer develop liver metastasis.
The open-label, multicenter Phase III study compared the efficacy and safety of DV versus Lapatinib plus Capecitabine in patients with HER2-positive advanced BCLM. A total of 104 patients, all previously treated with Trastuzumab and Taxanes, were enrolled, with 53 receiving DV and 50 receiving Lapatinib plus Capecitabine.
As of the data cutoff date (December 31, 2023), the Independent Review Committee (IRC) assessment showed that DV significantly improved progression-free survival (PFS) compared to Lapatinib plus Capecitabine (median: 9.9 months vs. 4.9 months; hazard ratio [HR]: 0.56 [95% CI: 0.35-0.90]). This was consistent with investigator-assessed PFS (HR: 0.62 [95% CI: 0.39-0.98]). While overall survival (OS) data were immature, they indicated a trend favoring DV. The safety profile of DV was consistent with prior experience, with no new safety signals detected.
Professor Wang noted, "This is the first confirmatory phase III study that demonstrated promising efficacy of an HER2-targeting ADC in patients with HER2-positive advanced BCLM." She added that DV demonstrated clinically meaningful benefit compared with Lapatinib plus Capecitabine and a manageable safety profile, potentially offering a promising new treatment option for patients with HER2-positive advanced BCLM previously treated with Trastuzumab and Taxanes.
The Biologics License Application (BLA) for this indication of DV has been accepted by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration in October 2024, and priority review was granted based on the breakthrough therapy designation.
