For many years, platinum-based chemotherapy has remained the standard first-line treatment for urothelial carcinoma, yet outcomes have remained suboptimal. As targeted therapies and immunotherapy continue to advance rapidly, there is growing demand for more effective precision treatment strategies.On May 21, 2026, the Chinese National Medical Products Administration (NMPA) officially approved toripalimab in combination with disitamab vedotin (DV) for the treatment of patients with HER2-expressing locally advanced or metastatic urothelial carcinoma, providing an important new therapeutic option.
At the same time, the recently released 2026 Chinese Society of Clinical Oncology (CSCO) Guidelines for Urothelial Carcinoma incorporated toripalimab plus disitamab vedotin as a Category I recommendation in the first-line setting and a Category III recommendation in the second-line setting, making it one of the most significant updates in this year’s guideline revision and establishing it as a preferred standard treatment option for Chinese patients.
This milestone reflects a dual breakthrough for a China-developed immunotherapy–ADC combination, both in terms of guideline recognition and clinical accessibility. It also highlights the strong confidence of Chinese experts in the regimen’s clinical value and enables domestic patients to benefit from a treatment approach that meets international standards of care.
Against this backdrop, Oncology Frontier – UroStream interviewed two experts deeply involved in the development of the 2026 CSCO Guidelines: Professor Xinan Sheng, Principal Investigator of the RC48-C016 study from Peking University Cancer Hospital, and Professor Cuijian Zhang of Peking University First Hospital, a member of the guideline writing committee. They discussed the significance of the new approval and guideline recommendations, reviewed the pivotal clinical evidence, and shared their perspectives on the future implementation of this treatment strategy in clinical practice.
Oncology Frontier – UroStream
Toripalimab plus disitamab vedotin is the first China-developed immunotherapy–ADC combination to receive a Category I recommendation for first-line treatment in the CSCO Urothelial Carcinoma Guidelines and was officially approved on May 21, 2026, for first-line treatment of urothelial carcinoma. What unmet clinical needs does this approval address for Chinese patients?
Professor Xinan Sheng
For Chinese patients with urothelial carcinoma, clinical practice has long been dominated by chemotherapy and, more recently, single-agent immunotherapy. Globally, however, first-line treatment has already entered the era of precision therapy based on immunotherapy–ADC combinations.
Although similar international regimens became available earlier, the approval of toripalimab plus disitamab vedotin, supported by findings from the RC48-C016 study, represents a particularly meaningful advance for Chinese patients.
Importantly, the efficacy data were generated in a Chinese patient population. This is highly valuable because Chinese patients differ from Western populations in genetic background, pathological characteristics, and treatment response patterns. As a result, evidence generated from Chinese-developed therapies provides a more relevant and practical foundation for clinical decision-making in China.
In addition, both toripalimab and disitamab vedotin have already accumulated extensive clinical experience in China and are relatively accessible, enabling more patients to benefit from innovative treatment.
The approval of this indication marks the beginning of a new era of immunotherapy–ADC combinations in first-line urothelial carcinoma treatment in China and fundamentally reshapes the treatment landscape.
Beyond representing a milestone for Chinese drug innovation, this approval delivers a meaningful clinical advance by providing a treatment option that combines affordability, efficacy, and tolerability. Ultimately, it offers patients a greater chance of prolonged survival and improved outcomes.
Oncology Frontier – UroStream
The updated CSCO Guidelines recommend toripalimab plus disitamab vedotin as a Category I first-line recommendation and a Category III second-line recommendation. As both a guideline contributor and a clinician, what key evidence and practical considerations supported this recommendation, and how do you believe this historic update will influence urothelial carcinoma treatment in China?
Professor Cuijian Zhang
The decision to grant toripalimab plus disitamab vedotin the highest level of recommendation was based on robust high-level clinical evidence and its relevance to the needs of Chinese patients.
Most notably, the pivotal clinical findings were published in The New England Journal of Medicine, underscoring their significance within the field.
For first-line treatment, the recommendation was primarily based on the phase III RC48-C016 trial. The study demonstrated that toripalimab plus disitamab vedotin significantly outperformed platinum-based chemotherapy in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). In particular, the regimen produced unprecedented survival benefits among Chinese patients with HER2-expressing disease while maintaining a manageable and well-characterized safety profile.
Its combination of robust efficacy and favorable tolerability was a key reason for its recommendation.
For more than two decades, platinum-based chemotherapy has been the cornerstone of treatment for advanced urothelial carcinoma. The inclusion of toripalimab plus disitamab vedotin in the guidelines marks a historic transition from chemotherapy-dominated treatment toward precision combination therapy.
Regardless of whether a patient is eligible for cisplatin, this regimen provides a high-level evidence-based treatment option with strong efficacy and manageable toxicity.
Importantly, for cisplatin-ineligible patients, elderly individuals, and those with significant comorbidities, it represents the first Category I recommended chemotherapy-free regimen capable of delivering substantial clinical benefit, addressing a long-standing unmet need.
In the second-line setting, recommendations were informed by the RC48-C014 study, supporting use of the combination in patients who have progressed after chemotherapy. This reflects the increasingly sophisticated, precision-based treatment approach adopted by the guidelines.
As immunotherapy and ADCs become more widely used in the first-line setting, second-line treatment decisions are becoming increasingly complex. Through careful patient stratification, the guidelines help ensure that each patient receives the most appropriate therapy.
In addition to high-level evidence, guideline development also considers the realities of clinical practice in China. Because RC48-C016 was conducted primarily in Chinese patients, its efficacy and safety data are highly relevant to the domestic population and therefore may offer greater practical value than evidence derived solely from Western populations.
Furthermore, the first-line indication for toripalimab plus disitamab vedotin has now been approved, and both drugs are already widely available throughout China, facilitating rapid implementation in routine practice.
Oncology Frontier – UroStream
The guideline update is largely based on the phase III RC48-C016 study. As the principal investigator, could you summarize the clinical performance of toripalimab plus disitamab vedotin as first-line treatment for urothelial carcinoma?
Professor Xinan Sheng
RC48-C016 was an open-label, multicenter, randomized phase III clinical trial conducted in China comparing toripalimab plus disitamab vedotin with standard first-line gemcitabine plus platinum-based chemotherapy.
Notably, the regimen is approved for patients with HER2 expression of IHC 1+ or higher, substantially broadening the eligible patient population and potentially offering a long-survival, high-response, and well-tolerated treatment option to the majority of patients.
- Long Survival
The trial had dual primary endpoints of progression-free survival and overall survival.
In 2025, the results were presented during the Presidential Symposium at ESMO and simultaneously published in The New England Journal of Medicine, attracting widespread international attention.
The study demonstrated a median overall survival of 31.5 months in the toripalimab plus disitamab vedotin arm—approximately double that achieved with chemotherapy.
Median progression-free survival reached 13.1 months, corresponding to a 64% reduction in the risk of disease progression. These outcomes rank among the most impressive reported in urothelial carcinoma clinical trials.
- High Response Rates
The objective response rate reached 76.1%, representing the highest response rate reported to date among randomized phase III studies in urothelial carcinoma.
This means that a substantial majority of patients experienced meaningful tumor shrinkage. In addition, the median duration of response was 14.6 months, providing sustained disease control and helping build patient confidence throughout treatment.
- Favorable Tolerability
The safety profile of the combination was consistent with previous studies, and no new safety signals were identified.
Compared with traditional chemotherapy, the regimen reduced the incidence of myelosuppression and related toxicities by nearly 30%, while maintaining excellent tolerability.
The success of this combination stems from its complementary biological mechanisms.
While immunotherapy–ADC combinations have become a major focus of oncology research, not all combinations achieve meaningful synergy. Toripalimab plus disitamab vedotin clearly demonstrates a “1 + 1 > 2” effect, translating into significant improvements in both PFS and OS.
Toripalimab activates antitumor T-cell responses and promotes deep, durable immune-mediated tumor control, including the development of immunologic memory. Combined with the immunologic carryover effect associated with checkpoint inhibition, this mechanism contributes substantially to the impressive long-term survival outcomes observed in the study.
Overall, toripalimab plus disitamab vedotin continues to redefine clinical practice, establishing a new standard for first-line treatment of urothelial carcinoma in China while contributing a valuable Chinese innovation to the global field of genitourinary oncology.
Oncology Frontier – UroStream
As the guideline recommendations are translated into routine clinical practice, what advantages does this regimen offer in terms of accessibility, reimbursement potential, and patient affordability? How can access be further expanded so that more patients can benefit from this Chinese-developed treatment strategy?
Professor Cuijian Zhang
Historically, first-line treatment for urothelial carcinoma relied primarily on chemotherapy, with limited efficacy.
Although international studies have demonstrated the value of immunotherapy–ADC combinations, relatively few Chinese patients were included in those trials. Consequently, the emergence of China’s first domestically developed immunotherapy–ADC combination represents a major breakthrough.
Its rapid approval and inclusion as a top-tier recommendation in the CSCO Guidelines signify a transition from following international developments to helping lead them. More importantly, the regimen is tailored to the clinical realities and needs of Chinese patients.
One of its greatest strengths lies in supply-chain stability. Both drugs are independently developed and manufactured in China, making them less vulnerable to international logistics disruptions or geopolitical uncertainties. This helps ensure consistent nationwide availability and prevents situations in which a guideline-recommended therapy is difficult to access.
From a reimbursement perspective, toripalimab was the first domestically developed PD-1 inhibitor approved in China and already has multiple indications included in the National Reimbursement Drug List. Its price has therefore decreased substantially.
Disitamab vedotin also has strong potential for future reimbursement expansion. Once the newly approved first-line indication is incorporated into reimbursement programs, out-of-pocket costs for patients could be reduced significantly, making innovative treatment accessible to many more families.
Compared with imported alternatives, this Chinese-developed combination may offer meaningful advantages in affordability while maintaining world-class efficacy.
To improve access at the grassroots level, CSCO will continue to organize nationwide educational programs, guideline dissemination initiatives, and physician training activities. These efforts will help standardize treatment practices and ensure that patients treated in community and regional hospitals can receive care comparable to that available at major academic centers.
At the same time, domestic pharmaceutical companies maintain extensive nationwide distribution networks, enabling innovative therapies to reach municipal and county-level hospitals more rapidly.
Looking ahead, we will continue to support real-world research to generate long-term outcome data in Chinese patients, optimize treatment strategies, and work closely with healthcare authorities to expand reimbursement coverage for innovative indications.
Ultimately, our goal is to transform Chinese innovation into tangible patient benefit and further elevate the overall standard of urothelial carcinoma care in China.
About the Experts
Professor Xinan Sheng
Professor Cuijian Zhang
