Conference Summary: Academic Deep Dive
Editor’s Note: During a recent academic session, Dr. Tao Zihao from Peking University First Hospital presented the preliminary results of a Phase II study evaluating the efficacy and safety of Disitamab Vedotin (RC48-ADC) in combination with radiotherapy for the adjuvant treatment of Upper Tract Urothelial Carcinoma (UTUC). This study provides a potential new therapeutic strategy for high-risk UTUC patients who are cisplatin-ineligible or refuse conventional chemotherapy.
01 Research Background: Addressing Unmet Needs in High-Risk UTUC
Patients with high-risk UTUC face a significant risk of recurrence following Radical Nephroureterectomy (RNU). While cisplatin-based adjuvant chemotherapy is the current standard of care, a substantial proportion of patients are ineligible due to impaired postoperative renal function. Current alternatives, such as carboplatin or adjuvant immunotherapy, have shown limited or inconsistent benefits in the UTUC setting. Although adjuvant radiotherapy has demonstrated improvements in local-regional control, its impact on overall survival (OS) remains controversial. Given the robust efficacy of the HER2-targeted ADC Disitamab Vedotin (RC48-ADC) in advanced urothelial carcinoma, its integration with radiotherapy in the adjuvant setting represents a critical area of exploration.
02 Study Design: Focus on HER2 Expression and Cisplatin-Ineligible Populations
This is a single-center, open-label, non-randomized Phase II clinical trial. Eligible patients were required to meet the following criteria: • Pathology: Pathologically confirmed UTUC post-RNU. • High-Risk Features: pT2 with at least one additional high-risk factor, pT3-T4, or pN+. • HER2 Expression: Immunohistochemistry (IHC) score of 2+ or 3+. • Treatment Limitations: Patients must be cisplatin-ineligible (e.g., renal insufficiency) or have declined cisplatin-based adjuvant chemotherapy. The primary endpoint of the study is Disease-Free Survival (DFS).
03 Patient Enrollment: Distribution of Adjuvant and Surveillance Cohorts
As of the current data cutoff, 47 of the planned 60 patients have been enrolled: • Adjuvant Therapy Group (n=25): Received RC48-ADC in combination with radiotherapy. • Surveillance Group (n=22): Managed via standard postoperative observation. Within the adjuvant therapy group, 16 patients have completed the treatment protocol, while 9 patients remain on active treatment.
04 Efficacy Data: Significant Improvement in 1-Year DFS Rate
Preliminary data, with a median follow-up of 12 months, demonstrated a clear survival advantage for the adjuvant therapy cohort: • Recurrence/Metastasis Events: Only 1 event (local recurrence or distant metastasis) was recorded in the adjuvant therapy group, compared to 8 events in the surveillance group. • DFS Benefit: The 1-year DFS rate was 93% in the adjuvant therapy group versus 72% in the surveillance group. These initial findings suggest that the combination of RC48-ADC and radiotherapy significantly reduces the risk of early postoperative recurrence in high-risk patients.
05 Safety Profile: Favorable Tolerability and Controlled Toxicity
The safety analysis focused on Treatment-Related Adverse Events (TRAEs): • Severe Adverse Events: Only 2 patients (approximately 8%) in the adjuvant therapy group experienced Grade 3 or higher TRAEs. The safety profile of the combination regimen was consistent with previous reports for the individual modalities, with no unexpected or refractory toxicities observed.
06 Conclusion and Outlook: A Potential Paradigm Shift in UTUC Adjuvant Care
This study represents the first global investigation into the combination of an ADC and radiotherapy as an adjuvant strategy for UTUC. The preliminary results confirm that for high-risk, HER2-overexpressing, and cisplatin-ineligible UTUC patients, RC48-ADC plus radiotherapy offers significant potential to improve 1-year DFS with a manageable safety profile. As enrollment continues, long-term DFS and definitive OS data are eagerly anticipated to further validate this regimen’s role in the postoperative management of UTUC.
