Abstract
Disitamab vedotin (RC48) is a novel cleavable antibody-drug conjugate (ADC) that has shown promising preclinical activity in HER2-positive breast cancer. However, real-world data regarding its efficacy and safety is lacking, especially in patients previously treated with trastuzumab and heavily treated patients. This retrospective study aimed to evaluate the effectiveness and safety of RC48 in HER2-positive metastatic breast cancer (MBC) in non-clinical trial settings. Eighty-one patients with metastatic HER2-positive BC who received RC48 in Shandong Cancer Hospital and Institute between September 2021 to November 2022 were included in this study. The primary endpoints were real-world progression-free survival (RWPFS) and objective response rate (ORR), and the secondary endpoints included safety and exploratory subgroup analyses. Results showed that the median RWPFS was 5.9 months, and the ORR was 29.6%, including one patient who achieved complete remission. Two-thirds of the patients had received more than one line of prior anti-HER2 treatment, and 76.6% were exposed to anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Patients who received RC48 in ≤3 lines of treatment had significantly longer RWPFS than those who received it in ≥4 lines of treatment. The median RWPFS of RC48 in patients with trastuzumab resistance and refractoriness was 6.5 months and 5.6 months, respectively. The sequence of pyrotinib and RC48 did not influence their total efficacy. To conclude, RC48 exhibited promising efficacy in HER2-positive MBC with manageable toxicity, particularly in patients previously treated with trastuzumab and those who had undergone extensive treatment. RC48 exhibited potent activity for patients regardless of trastuzumab resistance or refractory. The sequence of pyrotinib and RC48 did not influence their total efficacy, indicating no cross-resistance.