(UroToday.com) At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster discussion session focused on Kidney and Bladder cancers on Saturday evening included a presentation from Dr. Huayan Xu on the role of combined treatment of advanced urothelial carcinoma (UC) using a combination of a HER-2 targeted antibody-drug conjugate and immunotherapy.
For patients with metastatic urothelial carcinoma (UC), platinum-based chemotherapy remains the first-line treatment of choice for patients who are eligible. Despite being the guideline-recommended approach, most patients will have disease progression following platinum-based chemotherapy. Immunotherapy using single agent immune checkpoint inhibitors is a standard, guideline-recommended second line treatment. However, the anti-HER-2 antibody-drug conjugate RC48-ADC (Disitamab Vedotin) has shown promising data in HER2-positive patients with locally advanced or metastatic UC who have progression following treatment with platinum-based chemotherapy. Interestingly, in these trials, some patients with evidence of HER2-positive immunohistochemistry (IHC 2+) but negative FISH test still benefited from the treatment of RC48-ADC. Thus, the authors sought to assess the efficacy and safety of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma (UC).
To do so, they performed an open-label, single-center, single-arm, phase II trial (NCT04073602). The authors enrolled patients with histologically confirmed urothelial carcinoma who received at least one prior systemic treatment. Patients further had to have evidence of HER2-negative disease (IHC 0 or 1+) and ECOG performance status of 0 or 1. Patients received RC48-ADC 2mg/kg every two weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
The primary objectives were activity (ORR) and safety with additional second objectives including progression-free survival, disease control rate and overall survival.
With a data cutoff of February 2022, 19 patients had been enrolled. The median age was 64 years (range 36 to 77 years). The majority (n=15; 79%) of patients had received two or more lines of treatment and 13 had visceral metastases. At baseline, 6 patients had HER2(IHC 0) and 13 had HER2(IHC 1+).
All patients (n=19) patients were assessable for response: the objective response rate was 26.3% (95% CI 9.1% to 51.2%) and the DCR was 94.7% (18/19). All six patients with HER2(0) had evidence of stable disease whereas the ORR was 38% (5/13) in patients with HER2(IHC 1+). Further, when stratified by clinical characteristics, the ORR was 31% (4/13) in patients with visceral metastasis, 17% (1/6) in those with liver metastasis, and 27% (4/15) in patients who had received at least 2 prior lines of treatment.
The median progression-free and overall survival were 5.5 months (95% CI 3.9 to 6.8) and 16.4 months (95% CI 7.1 to 21.7), respectively.
Common treatment-related AEs were leukopenia (52.6%), hypoesthesia (47.4%), alopecia (47.4%), AST increase (42.1%), ALT increase (42.1%), and neutropenia (42.1%), fatigue (42.1%), nausea (26.3%), vomiting (15.8%). Most of these AEs were Grade 1 or 2 though a grade 3 neutropenia event was noted in two patients (10.5%). A single serious adverse event was seen with CPK increase (5.3%).
Thus, the authors conclude that this phase II trial demonstrates that RC-48-ADC is safe and has evidence of activity in HER-negative patients with locally advanced or metastatic urothelial carcinoma.
Presented by: Huayan Xu, MD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Oncology， Peking University Cancer Hospital & Institute, Beijing, China