Editor’s Note: Urothelial carcinoma is one of the most common malignant tumors in the urinary system, and its treatment strategies have undergone many changes in recent years. Although traditional chemotherapy has played a significant role in the treatment of urothelial carcinoma, the development of new drugs such as immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) has brought about new breakthroughs in treatment. At the recent 2024 CSCO Guidelines Conference, “Oncology Frontier” was fortunate to invite Professor Chuanliang Cui from Peking University Cancer Hospital to provide an in-depth interpretation of the key updates to the 2024 CSCO urothelial carcinoma guidelines.
“Oncology Frontier”: What are the major updates in the 2024 urothelial carcinoma guidelines? What impact does the combined ADC immunotherapy strategy have on clinical practice?
Professor Chuanliang Cui: In the field of urothelial carcinoma treatment, this year’s major updates focus on first-line and subsequent treatment strategies. In October 2023, data from an international multicenter study on pembrolizumab combined with enfortumab vedotin (EV) as a first-line treatment for urothelial carcinoma was presented at the ESMO conference, with significant participation from Chinese research centers. The study results showed that compared to traditional gemcitabine and platinum-based chemotherapy, pembrolizumab combined with EV exhibited significant advantages in several key indicators, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), where OS notably extended from 16.1 months to 31.5 months. Given the significant improvement in efficacy demonstrated by pembrolizumab combined with EV in the first-line treatment of urothelial carcinoma, the NCCN guidelines have already updated this combination as the preferred first-line treatment in their 2024 second edition. Additionally, considering that EV is expected to be approved in China soon, this drug combination is likely to become an accessible option domestically and is expected to be officially included in the first-line treatment recommendations for urothelial carcinoma in this year’s CSCO guideline update—a particularly important change in this update. As the first-line treatment updates, changes to second-line and third-line treatment strategies may also occur. The traditional gemcitabine combined with platinum chemotherapy regimen, previously a key component of first-line treatment, might shift to an important recommended option for second-line therapy. Due to the extensive evidence-based medical data accumulated by chemotherapy in the treatment of urothelial carcinoma, it continues to hold a significant place in treatment protocols. Moreover, antibody-drug conjugates (ADCs) targeting different antigens, such as sacituzumab govitecan (SG), due to their lack of cross-resistance with EV, could become significant recommendations for second-line therapy. Additionally, targeted drugs like those targeting FGFR may also become important choices for second-line therapy. Although FGFR targeted drugs are not yet available in China, ongoing clinical trials may soon offer more treatment options to patients. With the establishment of immune combination with ADC as the standard first-line treatment, clinical research in the subsequent lines of treatment will also become a significant area of development. These studies may include new immune checkpoint inhibitors, immune combination therapies, immune combined with targeted therapy, and immune combined with ADC and other targeted drugs or chemotherapy. As data from these studies continue to be updated, they will provide more treatment options and evidence-based medical evidence for patients with urothelial carcinoma in second-line and higher treatments.
References
T.B. Powles, B. Perez Valderrama, S. Gupta, et al. EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). ESMO 2023; LBA6.
