Future Treatment Options for Advanced Bladder Cancer

Transcript:Thomas Powles, MBBS, MRCP, MD: In bladder cancer, durvalumab is being developed alone, but also in combination with tremelimumab. And it’s my personal opinion that we use the second-line cisplatin-refractory data space as a ground to helping patients, but developing drugs.

The proportion of patients we’re benefiting at this stage is modest—20% to 30% response rates with a biomarker on all-comers. And those patients, who respond, do well. But when one gives these drugs in combination with other agents we’ve seen in other tumor types like melanoma—CTLA-4 with tremelimumab—you can see higher response rates. We haven’t yet seen data of durvalumab and tremelimumab together, but we hope to increase the response rates by somewhere in the region of 50%, which would be great. And then this combination is being tested against standard chemotherapy in the frontline setting in the DANUBE study.

This trial would be the first frontline randomized trial to read out with immune checkpoint inhibitors. It would be the first frontline randomized trial to read out for a very long time, if it was positive to change practice. But I think really importantly there is a chance that immune therapy will supersede chemotherapy. Some of the work that we’ve done has shown that if you give immune therapy, and those patients fail and you sequence chemotherapy, patients respond to the subsequent chemotherapy. Some people say they respond better, but I don’t really have any evidence for that.

But what we do have evidence for is what I think is a lack of cause resistance. So, sequencing these drugs is going to be incredibly important in the future. But in the 5 years’ time that we see new patients, I hope we test them for biomarkers, but I’m not convinced by that yet. We see patients, we test them for biomarker, they get immune therapy first. If that works, they continue. If that doesn’t work, they switch across to standard chemotherapy, and we’d like to be pushing those overall survival curves 20%, 30%, 40% or 50% in the right direction, but also the tail of the curve is really important.

We know in the second-line space, atezolizumab, durvalumab, other drugs can achieve long-term durable remissions, but maybe in only 20% of patients. And what I’d like to see is us getting much closer to 50%. It’s my personal opinion that combination therapy is going to be required in the frontline setting to achieve that.

So, I’m really excited about what’s happening in bladder cancer at the moment. We are going through a period of dynamic change of huge amounts of academic research, literally thousands of patients on trials for the first time. We are going to discover more about immune combinations soon. We’re going to discover more about chemotherapy combinations soon. There’s also a really nice trial looking at a biomarker analysis and then targeted therapy depending on that biomarker with immune checkpoint inhibitors and with durvalumab. And that trial, called BISCAY, is another piece of the jigsaw puzzle for the future. It’s very likely, in my opinion, that at least one of these avenues is going to prove very effective in patients who really change the outcome for this very, very nasty disease.

Transcript Edited for Clarity