2024 SABCS: Phase III Disitamab Vedotin Study Results for HER2-Positive Breast Cancer with Liver Metastasis

In YANTAI, China, on December 12, 2024, during the "Novel HER2 Therapeutics" Poster Spotlight Session at the 47th San Antonio Breast Cancer Symposium (SABCS), RemeGen Co. Ltd. unveiled pivotal findings from their phase III clinical trial (RC48-C006, NCT03500380) on Disitamab Vedotin (DV). This trial focuses on treating patients afflicted with HER2-positive advanced breast cancer paired with liver metastasis (BCLM). Notably, this marks the first global prospective randomized phase III study spotlighting a HER2-targeting antibody-drug conjugate (ADC) and demonstrating significant efficacy in addressing HER2-positive advanced BCLM. Professor Jiayu Wang from the Cancer Hospital, part of the Chinese Academy of Medical Sciences, led the presentation and subsequent discussion of this groundbreaking study. The SABCS stands as a preeminent annual conference, showcasing the forefront of clinical research in breast cancer, and the RemeGen-sponsored study garnered significant international attention.

An alarming statistic reveals that approximately 45% of patients with HER2-positive advanced breast cancer suffer from liver metastasis, facing a dire prognosis with a dismal 5-year survival rate ranging between 8% and 12%. Current therapeutic options for this subgroup remain unsatisfactory, underscoring the critical need for more effective interventions.

The study undertaken was a randomized, open-label, multicenter phase III trial, evaluating the efficacy and safety of DV against the combination treatment of Lapatinib plus Capecitabine in patients with HER2-positive advanced BCLM. The trial enrolled a total of 104 participants, dividing them into two groups: 53 receiving DV and 50 undergoing treatment with Lapatinib plus Capecitabine. All participants had a treatment history involving Trastuzumab and Taxanes.

Data collected up to the cutoff date of December 31, 2023, revealed that, as assessed by the Independent Review Committee (IRC), DV significantly enhanced progression-free survival (PFS) in comparison to Lapatinib plus Capecitabine, showcasing a median PFS of 9.9 months versus 4.9 months. This improvement was quantified with a hazard ratio (HR) of 0.56, with a 95% confidence interval (CI) ranging from 0.35 to 0.90, aligning closely with the investigator-assessed PFS (HR: 0.62 [95% CI: 0.39-0.98]). While the overall survival (OS) data remains immature, initial trends suggest a favorable outcome with DV. The safety profile of DV remains consistent with prior usage, with no novel safety concerns emerging.

Professor Jiayu Wang remarked on the study's outcomes, highlighting it as the first confirmatory phase III trial demonstrating the promising efficacy of a HER2-targeting ADC in patients with HER2-positive advanced BCLM. DV not only presented clinically meaningful benefits over Lapatinib plus Capecitabine but also maintained a manageable safety profile. This potentially positions DV as a promising new therapeutic option for patients who have previously been treated with Trastuzumab and Taxanes. Moreover, a Biologics License Application (BLA) for this indication of DV has already been accepted by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration as of October 2024. The application has been granted priority review, bolstered by the designation of DV as a breakthrough therapy.