Highlights on urothelial cancer
Prof Christof Vulsteke, medical oncologist at the Integrated Cancer Center, Ghent, provides his selection of highlights on urothelial cancer from ASCO GU 2024.
The UNITE study was a very small study in patients with advanced urothelial carcinoma treated with enfortumab vedotin (EV) after platinum-based therapy and maintenance avelumab. The study outcomes demonstrated concordance with existing data on EV efficacy in platinum-based therapy and checkpoint inhibitor-refractory advanced urothelial carcinoma. These findings substantiate the utilization of EV as a viable option for third-line therapy following disease progression during maintenance avelumab treatment.
The ANTICIPATE study is a small phase II trial for patients with newly diagnosed MIBC for whom radical cystectomy is planned, and who are cisplatin ineligible or refuse cisplatin based neoadjuvant chemotherapy. Within this trial, patients were subjected to neoadjuvant therapy involving tislelizumab, in combination with APL-1202, a MetAP2 inhibitor available in oral form, exhibiting anti-angiogenic and anti-tumor properties. The trial yielded a pathological complete response rate of 21% when tislelizumab was administered as a sole intervention, and a notable increase to 39% when utilized in combination with APL-1202. Consequently, the observed outcomes suggest the potential merit of further investigating this therapeutic regimen in a larger phase III clinical trial.
At ASCO GU, several subgroup analyses of the EV-302 trial were presented. The observed benefits remained consistent across specific pre-determined subgroups. These subgroup analyses complement the primary analysis findings, reinforcing the notion that EV+P has the potential to emerge as a novel standard of care for first-line treatment of locally advanced or metastatic urothelial carcinoma.
The PemCab study, a limited-scale phase II trial, explored the addition of cabozantinib to pembrolizumab as a first-line therapeutic approach for patients with advanced urothelial carcinoma ineligible for cisplatin. The trial revealed an overall response rate of approximately 45%, coupled with a median overall survival of 17 months. While these results suggest potential avenues for further investigation, it is noteworthy that cabozantinib is associated with notable toxicity. Given the anticipated introduction of the combination therapy comprising EV and pembrolizumab for urothelial cancer, a pertinent consideration emerges regarding the potential extension of this approach to include a TKI in conjunction with pembrolizumab.
In the landscape of MIBC, pertinent clinical trials have emerged with divergent outcomes. Specifically, the IMvigor 010 trial yielded unfavorable results in the adjuvant setting, while in contrast, the Checkmate 274 trial demonstrated positive findings. The AMBASSADOR trial,evaluating pembrolizumab as adjuvant therapy in patients with high-risk MIBC following surgical resection is the judge out there.
The primary endpoint of disease-free survival was positive and improved from 14 to 29 months. However, it is pertinent to acknowledge the absence of overall survival benefits in this clinical setting. Consequently, the emergence of two trials with concordant findings, elucidating a prolonged disease-free survival without concomitant improvements in overall survival, introduces a challenging dimension in patient discussions.
References:
Nizam A et al, 2024, Outcomes in patients (pts) with advanced urothelial carcinoma (aUC) treated with enfortumab vedotin (EV) after switch maintenance avelumab (MAv) in the UNITE study. J Clin Oncol 42, S4; 537
Galsky M et al, 2024, Oral APL-1202 in combination with tislelizumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC): Interim analysis of ANTICIPATE phase II trial. J Clin Oncol 42, S4; 632
van der Heijden MS et al, 2024, Enfortumab vedotin (EV) in combination with pembrolizumab (P) versus chemotherapy in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC): Subgroup analyses results from EV-302, a phase 3 global study. J Clin Oncol 42, S4; LBA530
Jain RK et al, 2024, Cabozantinib plus pembrolizumab as first-line therapy for cisplatin-ineligible advanced urothelial carcinoma (PemCab). J Clin Oncol 42, S4; 539
Apolo AB et al, 2024, AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation.J Clin Oncol 42, S4; abstr LBA531
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