We presented a pair of phase III clinical trials for a novel investigational agent called UGN-102. The two studies that were presented, one was called ATLAS, this was a phase III randomised clinical trial between the study drug, which is used in a space called low-grade intermediate-risk non-muscle invasive bladder cancer, randomising the study drug to  TURBT as a primary treatment for bladder cancer. The second study was ENVISION, which was another phase III study, single arm, looking at using this study agent in patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer.

What was the study design?

ATLAS, again, was a randomised controlled trial. The study drug itself, UGN-102, is a reverse thermal gel containing mitomycin. This is a gel that is instilled into the bladder, so this is called intravesical therapy, it’s given via traditional urethral catheter. This gel coats the lining of the bladder and actually can dissolve away tumours, this is a process called chemoablation. So ATLAS was to compare this drug being given once a week for six weeks as a primary treatment for bladder cancers, essentially trying to melt them away with topical treatment, comparing it to the standard of care which we’ve done for many decades which is TURBT which is actually to resect the tumours surgically.

So that’s the study design for ATLAS, ENVISION is a single-arm study where all 240 patients received the study drug. Patients received the drug once a week for six weeks and, again, clearance of the tumour was ascertained at cystoscopy at three months and then patients were followed up to a year to assess the durability of response.

What were the results of this study?

So for ATLAS, which was the phase III study, we looked to see a comparison between tumour resection, again the standard of care, versus the novel agent performing chemoablation. When we assessed the outcome at three months, which was to see if any tumour was remnant or recurrent at three months, basically the two groups were essentially even. The TURBT group 64% of patients demonstrated a complete response and in the study arm 65% of patients demonstrated a complete response. So really notably the topical chemoablation, which avoided surgical intervention, so no anaesthesia, no discontinuing blood thinners, demonstrated essentially an equivalent if not slightly superior complete response rate at three months. It’s really the durability of response at 12 months where we begin to see the two curves separate, again favouring the study drug.

When we look at 12 month durability of response the estimated durability of response by Kaplan-Meier analysis in the TURBT group was 68% and in the study group with UGN-102 the estimated durability of response at 12 months was 80%. So we’re seeing that over time there appears to be a more durable difference in cancer control with tumours not seen in the bladder in the majority of patients who are complete responders.

In ENVISION we sub-selected patients who were recurrent and they could either have large or small tumours, they could have multifocal or unifocal tumours. Here the complete response rate was even more robust – 79.6% of patients had a complete response at three months and the estimated probability of remaining in that complete response at 12 months by Kaplan-Meier analysis was 82.3%. So, again, we’re seeing a very robust initial treatment response where almost four out of five patients have their tumour completely chemoablated away at thee months and then the vast majority of those patients at 12 months maintain that complete response, showing a durable efficacy of this topical agent in the absence of any surgical intervention.

What is the clinical significance of these results?

So historically we have been managing this type of tumour, low-grade intermediate-risk non-muscle invasive bladder cancer through TURBT, meaning we go into the operating room, we put patients under anaesthesia, we have to hold their blood thinners and they go to the operating room and have these tumours surgically excised. This has been the standard of care for many decades. This is really a paradigm shift, potentially, in offering a non-operative intervention where patients do not have to go under anaesthesia or stop blood thinners but simply have an office-based treatment to instil a medication into the bladder that actually allows the tumours to primarily dissolve away and be treated. So, again, this is a complete shift. We have never had this notion of chemoablation previously in the management of bladder cancer and what we’re finding is not only are we seeing a very strong initial efficacy at three months, even superior to that of resection, but we’re seeing that the durability of response is even more prolonged than we can achieve now surgically. So, again, we’re not seeing just an alternative but we’re seeing potentially a superior treatment to TURBT, both in terms of initial response and durability. So, again, were this drug to be approved, you would see a very new tool in the armamentarium of urologists to treat this sort of nuisance disease that recurs frequently in the bladder and can lead to comorbidity for patients who have to undergo anaesthesia in older age or with cardiopulmonary disease which is very common in our bladder cancer patients.

Is there anything you would like to add?

No, again, the importance of this is really just … its significance is really across all of urology. All urologists manage this disease space – low-grade intermediate-risk non-muscle invasive bladder cancer. So, again, when we have treatments that potentially shift the paradigm for the way in which this disease is managed, the implications across our entire field are pretty profound.