Disitamab vedotin (RC48) long-term regimen in a post-nephroureterectomy patient with metastases: a case report.

Background: For patients with metastatic upper tract urothelial carcinoma (UTUC), the preferred first-line treatment is platinum-based chemotherapy. Immunotherapy can be considered a subsequent treatment if the chemotherapy is ineffective or the disease progresses. However, how should treatment be administered if immunotherapy is useless and the patient cannot take chemotherapy? Especially in patients who have metastasized after radical nephroureterectomy (RNU). Case presentation: A 68-year-old woman was admitted to the hospital due to left flank pain for two weeks and was diagnosed with metastatic UTUC after RNU. The patient underwent systemic chemotherapy with gemcitabine and cisplatin (GC), as well as reduced-dose GC, but developed myelosuppression. Immunotherapy was ineffective, so Disitamab vedotin (RC48) was chosen. Results: Disitamab vedotin (RC48) monotherapy was administered for 13 cycles, during which thyroid function remained normal, the patient responded well to the treatment, and the disease was controlled well. In the subsequent two years of follow-up, there was no disease recurrence. Conclusion: The long-term treatment regimen with RC48 is feasible for metastatic UTUC after RNU, and RC48 monotherapy is suitable as first-line therapy for selected patients.

Development and validation of bioanalytical methods to support clinical study of disitamab vedotin.

Disitamab vedotin (RC48), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), is the first antibody-drug conjugate in China with an approved biological license application. A bioanalytical method was established for three analytes (total antibody, conjugate antibody and free payload) to help characterize their pharmacokinetic behavior in clinical settings. The bioanalytical methods were validated according to M10 guidance. Electrochemiluminescence assay methods were used for the quantitative measurement of total antibody and conjugated antibody in human serum. A LC-MS/MS method was used to quantify the concentration of MMAE in human serum. The method had high specificity and sensitivity with a quantitative range of 19.531-1250.000 ng/ml (total antibody), 39.063-5000.000 ng/ml (conjugated antibody) and 0.04-10.0 ng/ml (MMAE), respectively.

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mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation.

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients with HER2-low metastatic breast cancer (MBC). We performed a systematic review to investigate the rechallenge treatment concept in the field of HER2-low MBC treatment and utilized a series of cases identified in the literature to illustrate the concept. Here we reported two clinical cases of HER2-low MBC patients whose disease progressed after prior treatment with MTAs such as docetaxel and vincristine. When rechallenged with disitamab vedotin ((RC48-antibody-drug conjugate (ADC), a monomethyl auristatin (MMAE) MTA)), both patients achieved a partial response and the final progression-free survival (PFS) was 13.5 and 9 months, respectively. Genomic profiling detected a PIK3CA H1047R mutation in the patients. The patients were treated with everolimus before being rechallenged with RC48, which may lead to a better response. This study further summarizes and analyzes the potential mechanism of the PI3K-AKT signaling pathway in MTA resistance and reveals that the PIK3CA H1047R mutation may be a potential molecular marker for the efficacy prediction of mTOR inhibitors, providing new insights and potential therapeutic strategies for the application of MTAs to MBC patients.

Disitamab Vedotin (RC48) for HER2-positive advanced breast cancer: a case report and literature review.

Background/aim: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with a higher risk of metastasis and poorer overall survival (OS) due to HER2 gene overexpression/amplification. Although anti-HER2 targeted therapy has shown survival benefits in HER2-positive advanced breast cancer (ABC) patients, long-term treatment often leads to drug resistance, complicating further treatment options. RC48, an antibody-drug conjugate (ADC), combines the benefits of antibody targeting with the cytotoxic effects of a small molecule drug. Case report: We present a case involving a female patient with HER2-positive ABC who developed drug resistance and disease progression following multi-line anti-HER2 targeted therapy. In this instance, RC48 exhibited anti-tumor activity in an ABC patient resistant to HER2-targeted therapy. After eight treatment cycles with 120 mg of RC48, the tumor size decreased and stabilized. Conclusion: This case report underscores the potential clinical value of RC48 as a promising treatment alternative for patients resistant to HER2 targeted therapies.