Trastuzumab Deruxtecan as a Salvage Therapy after Disitamab Vedotin Failure in HER2 Altered Solid Tumors: A Preliminary Real-world Comparative Study

Abstract

Background & Objective: To compare the efficacy and safety of two human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugates (ADCs), disitamab vedotin (RC48) and trastuzumab deruxtecan (DS-8201), in patients with the HER2 altered solid tumors.

Methodology: We conducted a preliminary real-world comparative study, which included a case of a patient with HER2 exon 20 insertion mutated lung adenocarcinoma and a retrospective analysis of 18 patients treated at Air Force Medical Hospital, PLA, Beijing between 2021 and 2025. Patients received either RC48 (n=12) or DS-8201 (n=6). The primary endpoints were objective response and adverse events, evaluated using RECIST 1.1 criteria and standard toxicity assessments.

Results: The case patient exhibited primary resistance and severe gastrointestinal toxicity to RC48 but achieved partial remission (PR) with DS-8201. In the cohort analysis, DS-8201 demonstrated a significantly superior PR of 66.67% compared to 8.33% for RC48 (P = 0.022). The adverse event profiles differed notably: DS-8201 was primarily associated with elevated transaminases and fatigue, while RC48 more frequently caused myelosuppression and hyperbilirubinemia.

Conclusion: DS-8201 demonstrates potential as one of the effective salvage therapies following RC48 failure in HER2 altered solid tumors, showing significantly better disease control and a distinct, manageable toxicity profile. These findings highlight the importance of selecting personalized ADCs based on molecular subtypes and toxicity factors and provide a basis for future, larger-scale prospective studies.