Trastuzumab Deruxtecan as a Salvage Therapy after Disitamab Vedotin Failure in HER2 Altered Solid Tumors: A
Lihong Wang1, Xuanye Lian2, Qijing Guo3
1Lihong Wang, Ph.D., Department of Oncology, Air Force Medical Center, PLA, Beijing 100142, China.
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.
Insights
Trastuzumab deruxtecan (DS-8201) shows superior efficacy and a manageable safety profile compared to disitamab vedotin (RC48) in HER2-altered solid tumors, offering a promising salvage therapy option.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- HER2-altered solid tumors represent a significant challenge in cancer treatment.
- Antibody-drug conjugates (ADCs) targeting HER2, such as disitamab vedotin (RC48) and trastuzumab deruxtecan (DS-8201), offer novel therapeutic strategies.
- Comparative real-world data on these ADCs are crucial for optimizing treatment selection.
Purpose of the Study:
- To compare the clinical efficacy and safety of RC48 and DS-8201 in patients with HER2-altered solid tumors.
- To evaluate treatment outcomes in a real-world setting, including a case of lung adenocarcinoma with HER2 exon 20 insertion.
- To identify potential differences in response rates and toxicity profiles between the two HER2-targeting ADCs.
Main Methods:
- A preliminary real-world comparative study including one case and a retrospective analysis of 18 patients.
- Patients received either RC48 (n=12) or DS-8201 (n=6).
- Objective response (RECIST 1.1) and adverse events were primary endpoints.
Main Results:
- DS-8201 achieved a significantly higher objective response rate (66.67%) compared to RC48 (8.33%) (P=0.022).
- The case patient resistant to RC48 showed partial remission with DS-8201.
- DS-8201 toxicity included elevated transaminases and fatigue; RC48 was associated with myelosuppression and hyperbilirubinemia.
Conclusions:
- DS-8201 demonstrates superior efficacy and a distinct, manageable toxicity profile compared to RC48 in HER2-altered solid tumors.
- DS-8201 shows potential as an effective salvage therapy after RC48 failure.
- Personalized ADC selection based on molecular subtypes and toxicity is important for future cancer treatment strategies.
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