I had the opportunity to discuss the SunRISe-4 trial and specifically the perioperative outcomes from this trial. This is a randomised controlled trial comparing patients who are cisplatin ineligible or cisplatin refusing with muscle-invasive bladder cancer, looking at a neoadjuvant strategy of cetrelimab, which is a PD-1 inhibitor, alone in the neoadjuvant setting, compared to cetrelimab with the TAR-200 device which is a device that’s put in the bladder that elutes chemotherapy in a sustained fashion.

Specifically, the presentation today was based on an interim analysis – 76 patients – looking at the surgical safety and also the change in function status of patients receiving this novel neoadjuvant therapeutic regimen and comparing the cetrelimab arm alone to the intervention arm, which was the combination arm.

What were the results of this study?

We found a few things and I think the background here that’s really critical is that whenever we’re looking at a neoadjuvant therapy strategy we need to prove not only that it works, and the efficacy data we are waiting on the final analysis, but the preliminary data that was presented at ESMO showed that the pathologic complete response rate with this drug regimen does appear to be doubled with the combination arm compared to cetrelimab alone. But we also need to demonstrate that it’s not going to be dangerous, it’s going to be safe and it’s also not going to decrease physical function in such a way that would either delay time to cystectomy or prevent patients from getting the definitive treatment for their bladder cancer.

So the very high-level summary is that we noted that, one, in patients receiving either the combination arm or the monotherapy arm the toxicity was relatively limited in so much as the major complication profiles were mostly grade 1-2, which is low-grade urinary toxicity. The time to cystectomy, the average time the patients took to go to cystectomy, what we call the median time to cystectomy, was 13 weeks. So in the vast majority of patients, 88%, they received their cystectomy on time per the protocol-specified time period which means that the therapy wasn’t preventing patients from or delaying patients getting the surgery that they needed.

Then we also looked at surgical complications and surgical complications were similar in both arms. So adding the gemcitabine eluting TAR-200 device, which was exposing patients to chemotherapy locally, did not increase surgical complication rates at either 30 days or 90 days. There were no deaths in the intervention arm within that first 30 days after surgery and ultimately now, of course, we’re moving into… we expect the final analysis in the coming years where they will look at the entire 160-person cohort which has been fully accrued and we’re just waiting on that analysis.

What is the clinical significance of these results?

The current guideline recommended treatment for muscle-invasive bladder cancer is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. Unfortunately, cisplatin-based neoadjuvant chemotherapy is unable to be received by about half of all patients with bladder cancer because of comorbidities or functional status that precludes them from getting it. There are also a lot of patients who are not willing to receive cytotoxic chemotherapy. This is a novel neoadjuvant treatment paradigm that is given prior to surgery with the goal of not only trying to decrease the burden of cancer within the bladder but also potentially treat micrometastatic disease outside of the bladder to offer those patients who can’t get the standard of care another alternative option.

It is a promising strategy that at this point not only appears to be efficacious, based on the initial interim analysis but also appears to be safe and it does not decrease physical function in patients or result in increased surgical complications. Therefore, it is a very promising potential adjunctive therapy that would allow patients who can’t get the standard another alternative.