Episode 3: The SunRISe-1 study
Presented by Prof Emmanuel Seront (UCL Louvain) and Prof Christof Vulsteke (Maria Middelares Gent)
Professor Vulsteke from Maria Middelares Gent will discuss the SunRISE-1 study, presented at ESMO2023. This study is centred on NMIBC, diverging from the typical purview of urologists, as it excludes metastatic urogenital cancer and perioperative conditions.
The SunRISE-1 trial employs TAR-200, a pretzel-shaped intravesical device designed to gradually release the established drug gemcitabine. The drug is administered initially every 3 weeks for the first 24 weeks, followed by a 12-week interval thereafter. Inclusion in the SunRISE-1 trial is contingent upon non-responsiveness, denoting a recurrence of CIS within 12 months following adequate BCG therapy.
Initially featuring three arms, the trial administered TAR-200, the checkpoint inhibitor cetrelimab, and their combination separately. The study proceeded with TAR-200 monotherapy which exhibited efficacy, while cetrelimab, whether alone or in combination, displayed limited effectiveness.
Follow-up results from ESMO2023 reveal a 77% CRR with TAR-200 monotherapy. CRR was determined through biopsies and centrally assessed urine cytology at 24 and 48 weeks, indicating that approximately 80% of responders achieved a complete response, with most maintaining it for an extended duration. This contrasts starkly with historical findings of a 20% CRR on checkpoint inhibition.
In cases of BCG-unresponsive HR NMIBC, the conventional standard of care is radical cystectomy, significantly impacting comorbidity and QoL. TAR-200 monotherapy demonstrates promising results and proposes a potential alternative, primarily inducing mild local side effects such as mictalgia and urosepsis.
The efficacy of checkpoint inhibitors is under scrutiny by experts. The KN676 trial, involving BCG-naïve patients, showed that pembrolizumab did not demonstrate superiority. The role of checkpoint inhibitors needs careful evaluation, especially considering patients’ limited tolerance for systemic toxicity.
The TAR-200 device emerges as a promising alternative, paving the way for further advancements. The recently presented TAR-210 at ESMO2023 involves erdafitinib, administered intravesically, presenting a feasible and promising approach for delivering new drugs intralocally, minimizing bladder impact, and reducing systemic toxicity.
References:
Necchi A et al. (2023). Results from SunRISe-1 in patients (Pts) with bacillus Calmette–Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer (HR NMIBC) receiving TAR-200 monotherapy. Annals of Oncology 34 (S2): S1254-S1335.