#China #Yantai #Disitamab Vedotin #PD-1 Inhibitor #Urothelial Carcinoma

Exploring New Frontiers in Urothelial Carcinoma Treatment

In a significant advancement for treating locally advanced or metastatic urothelial carcinoma (la/mUC), the prestigious Annals of Oncology has published its long-term follow-up results from a clinical trial involving the combination of Disitamab Vedotin (DV) and Toripalimab. Published on January 7, 2025, these findings underscore the potential of this innovative approach in tackling a challenging cancer landscape.

Milestone in Cancer Treatment

This is the first instance of long-term data being published for HER2-targeted antibody-drug conjugate (ADC) in conjunction with PD-1 inhibitors for treating la/mUC. The results showcase a remarkable objective response rate (ORR) of 73.2%, coupled with a median overall survival (OS) of 33.1 months, surpassing previously reported figures from similar clinical studies. This trial, identified as NCT04264936, was supervised by esteemed professionals from Peking University Cancer Hospital, ensuring stringent protocols were followed in its execution.

Context of Urothelial Carcinoma

Urothelial carcinoma ranks as the sixth most commonly diagnosed cancer globally. The GLOBOCAN 2022 database reported approximately 614,298 new cases in 2021 along with 220,596 deaths, highlighting the critical need for effective treatment solutions. The rise of new therapeutic combinations, especially ADCs, has provided fresh hope as they deliver promising outcomes for patients diagnosed with this aggressive form of cancer.

As a HER2-targeted ADC, DV has already received approval in China for patients expressing HER2 who have undergone prior platinum-based chemotherapy, based on its performance in pivotal trials demonstrating an ORR of 50.5% and a median duration of response (DOR) of 7.3 months.

Clinical Trial Overview

The trial under review focused on the combination therapy of DV with Toripalimab, carried out in two phases. Initially, in phase 1b, two DV dosage levels (1.5 mg/kg and 2.0 mg/kg) were combined with a fixed dose of Toripalimab (3.0 mg/kg), determining the most effective phase 2 dosage. Between August 2020 and December 2021, 41 individuals, mainly over 60 years old, were enrolled. The participants had various prior treatment histories, including some with lung and liver metastases, showcasing the trial's real-world relevance.

Impressive Response Rates and Survival Benefits

The results as of March 1, 2024, were indeed compelling: the ORR stood at 73.2%, with nine patients achieving complete responses and 26 showing partial responses. Moreover, they recorded a DCR of 90.2%, and the median PFS was recorded at 9.3 months. After analyzing different subgroups, it was observed that patients with HER2 expression (IHC 1+/2+/3+) exhibited enhanced ORR and prolonged survival compared to those with lower expressions. For instance, chemotherapy-naïve patients showed an encouraging response rate of 76.0% compared to 68.8% for those who had previously undergone platinum therapy.

Conclusively, this combination therapy between DV and Toripalimab presents a promising frontier in the oral oncology realm. The observed response rates and overall survival benefits emphasize its potential applicability in clinical settings, encouraging further research and exploration into the full therapeutic landscape this combination could unlock for patients with la/mUC. These findings are not just clinical data; they symbolize hope for many grappling with this aggressive disease stage. This convergence of drug therapies marks a hopeful stride towards enhanced treatment options in urothelial carcinoma management, setting a new benchmark for patient care and therapy innovation.