Conference Summary: In-Depth Academic Analysis
Editor’s Note: At a recent academic symposium, Dr. Xuanjun Guo (Peking University First Hospital) presented data from a multicenter real-world study evaluating the efficacy and safety of Disitamab Vedotin (RC48), a humanized anti-HER2 antibody-drug conjugate (ADC), administered as monotherapy or in combination with PD-1 inhibitors for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). This study provides critical real-world evidence for patients seeking bladder-sparing alternatives.
01. Clinical Background: The Unmet Need in HR-NMIBC
High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is characterized by a significant risk of recurrence and progression. While intravesical Bacillus Calmette-Guérin (BCG) remains the standard of care (SoC), a substantial proportion of patients either fail to respond (BCG-unresponsive) or are unable to tolerate the treatment (BCG-ineligible). For these patients, radical cystectomy is the traditional recommendation; however, it profoundly impacts quality of life. Consequently, exploring effective systemic or targeted bladder-sparing therapies has become a priority in urological oncology.
02. Study Design: A Multicenter Real-World Exploration
This multicenter, retrospective, real-world study analyzed 32 patients with HR-NMIBC treated between June 2022 and December 2024. • Patient Baseline: Median age was 66 years. The cohort included 7 BCG-unresponsive patients and 25 BCG-ineligible/inappropriate patients. • Treatment Regimens: 3 patients received RC48 monotherapy, while 29 received RC48 combined with PD-1 inhibitors. Dosing schedules included every 2 weeks (Q2W) or every 3 weeks (Q3W). • Study Endpoints: The primary endpoint was the complete response (CR) rate at 3 months. Secondary endpoints included event-free survival (EFS), duration of complete response (DoCR), 6-month bladder preservation rate, and safety.
03. Efficacy Outcomes: Robust Clinical Remission and Survival
The study demonstrated that RC48-based regimens yielded positive results in both short-term remission and long-term survival: • Overall Response: At the 3-month assessment, 23 of the 32 patients achieved CR, representing an overall CR rate of 71.9%. • Subgroup Analysis: The CR rate reached 85.7% (6/7) in the BCG-unresponsive group and 68.0% (17/25) in the BCG-ineligible/inappropriate group. • Durability of Response: Among the 23 patients who achieved CR, the median DoCR was 16.9 months. • Survival Data: The median EFS for the entire cohort was 22.1 months. Statistical analysis showed no significant differences in EFS across subgroups defined by BCG status, treatment modality (monotherapy vs. combination), or dosing frequency (Q2W vs. Q3W).
04. Safety Profile: Manageable Adverse Events
Treatment-related adverse events (TRAEs) occurred in 53.1% of the patients. • Severity: Most TRAEs were Grade 1 or 2, with peripheral neuropathy and rash being the most frequently reported symptoms. • Severe AEs: Only 2 patients (6.3%) experienced Grade 3 or higher adverse events. Overall, systemic RC48 therapy demonstrated a favorable safety profile in the HR-NMIBC population, with no new safety signals identified.
05. Expert Discussion and Future Perspectives
During the discussion, Dr. Guo addressed the correlation between HER2 expression and efficacy. The study included patients with HER2 scores of 1+, 2+, and 3+. While no statistically significant correlation was found between HER2 expression intensity and CR rate or EFS—likely due to the limited sample size (n=32)—the targeted mechanism of the ADC remains a significant area of interest. Regarding the potential for intravesical administration (local instillation) of RC48, Dr. Guo noted that while systemic administration was the focus of this study, other clinical trials in China are currently evaluating intravesical RC48, with some already in Phase I stages.
Conclusion: Systemic therapy based on Disitamab Vedotin (RC48) shows promising preliminary activity and a manageable safety profile in HR-NMIBC patients who are BCG-unresponsive or ineligible. Larger prospective trials are warranted to confirm long-term durability and define the optimal role of this regimen in bladder-sparing protocols.
