Mini oral session: GU tumours, non-prostate

Professor Emmanuel Seront, medical oncologist at Cliniques Universitaires Saint-Luc in Belgium, provides a selection of highlights in urothelial and renal cancer from the mini oral session at ESMO.

There is an urgent unmet medical need for patients with high-risk, BCG-unresponsive NMIBC, as the standard treatment in these cases is radical cystectomy. However, new therapeutic approaches, such as TAR, offer promising alternatives. TAR delivers gemcitabine directly into the bladder in continuous cycles every three weeks. The SunRISe-1 trial randomised patients into three groups: TAR monotherapy, cetrelimab monotherapy or a combination of TAR and immunotherapy. Results demonstrated that TAR monotherapy had the highest efficacy, achieving an impressive 85% pCR. These findings represent a significant advancement in the management of high-risk NMIBC.

Moving on to MIBC, AMBASSADOR is a pivotal phase 3 study evaluating pembrolizumab in the adjuvant setting. Patients receive pembrolizumab for one year following radical cystectomy. Similar to previous findings with nivolumab, this trial demonstrated that pembrolizumab significantly improves DFS. However, OS data is still pending, as longer follow-up is needed. The results are promising, highlighting multiple trials that support the role of immunotherapy in reducing the risk of recurrence after radical cystectomy.

The VOLGA trial is another important study, particularly for cisplatin-ineligible patients. It investigates a neoadjuvant and adjuvant triplet regimen combining tremelimumab, durvalumab and EV in the perioperative setting. Patients receive all three agents before cystectomy, followed by tremelimumab and durvalumab post-surgery. The trial also investigated the link between ctDNA clearance and treatment response, revealing that patients with reduced ctDNA levels were more likely to achieve a pCR. Conversely, those without ctDNA clearance had a lower chance of reaching pCR.

In renal cancer, the TACITO trial evaluated the role of faecal microbiota transplantation (FMT) in combination with pembrolizumab and axitinib. In this prospective study, patients receiving this treatment combination were randomized to either receive FMT or not. The results showed that patients who received FMT had approximately double the ORR compared to those who did not receive FMT. These findings are highly encouraging and suggest that FMT could potentially enhance the efficacy of immunotherapy, warranting further investigation in future clinical trials.

In mUC, three key analyses have focused on improving patient selection for targeted therapies. In the EV-302 trial, Tom Powles presented a sub-analysis exploring the correlation between Nectin-4 expression and response to EV combined with pembrolizumab. The findings showed that the combination was superior to chemotherapy, regardless of Nectin-4 expression levels. 

Two other trials aimed to select patients based on FGFR mutations or HER2 protein expression. In a phase 2 trial, first-line treatment for mUC combined pembrolizumab with an FGFR inhibitor, futibatinib. Patients with FGFR alterations, primarily FGFR3 mutations, showed a higher response rate compared to those with FGFR wild-type tumours. The other trial investigated HER2-targeting ADC disitamab vedotin. This phase 2 trial enrolled around 20 patients with UC expressing HER2 and achieved a disease control rate of 95%.
These promising results pave the way for future trials to further refine patient selection and optimize treatment strategies in mUC.