Targeting Trop-2 in Advanced Urothelial Carcinoma - Episode 15

Future Directions in Advanced Urothelial Carcinoma

Drs Neeraj Agarwal and Petros Grivas comment on biomarkers and novel therapies under investigation for advanced urothelial carcinoma and remark on the next steps for treating patients with antibody-drug conjugates.

Petros Grivas, MD, PhD: The 1 important question is what the future is bringing to us. We’re still in a long pursuit of the Holy Grail of biomarkers of how to select our patients. FGFR2 or FGFR3 mutational fusion is a biomarker and target for erdafitinib. We discussed PD-L1, which is losing its space. What do you think about the future of biomarkers in this disease? Where do we have to make some progress?

Neeraj Agarwal, MD: We’re going to be selecting patients for therapies based on biomarkers in the near future. There are so many exciting abstracts that were presented at the 2021 ASCO [American Society of Clinical Oncology Annual Meeting]. The way the field is moving, it’s a matter of time. It’s beyond the scope of our discussion to talk about all those biomarkers, but we’ll definitely be dealing with all the biomarkers while making any treatment decisions in near future. That’s what I have to say on this.

Petros Grivas, MD, PhD: I agree. There’s so much ongoing research. We’ve seen data from different immunotherapy trials, including IMvigor130 with Dr Matthew Galsky and colleagues; the JAVELIN Bladder 100 trial with Dr Thomas Powles, myself, and others; and Dr Srikala Sridhar showing biomarker data. There’s a challenge standardizing the assays and time points across clinical trials, but it’s a great pursuit. It’s important to pursue more individualized metrics and tools in the decision of how to select the right patient for the right treatment, and for the right patient at the right time. That’s something that we keep working on.

The other important point I want to make is that having dialogue with the patient makes a big difference. Neeraj, you’ve mentioned this before in a different program. We’re here to help the patient make a decision and consult them about the other options they have, not dictate to them what the options will be. Having patient advocates in the design of clinical trials is also very important.

Neeraj Agarwal, MD: Absolutely.

Petros Grivas, MD, PhD: Do you have any last-minute remarks or thoughts before we say goodbye?

Neeraj Agarwal, MD: We had a great discussion. Thanks for having me. There’s great, exciting news coming for our patients on a monthly basis. For me, the most exciting class of drugs in patients with metastatic bladder cancer are antibody-drug conjugates. It’s a matter of time. They’ll move to first-line therapy, and the neoadjuvant and adjuvant therapy settings, and they’ll become the new backbones for combinatorial regimens down the line. That’s my take on the field.

Petros Grivas, MD, PhD: This is a very important observation. To your point, there are trials looking at antibody-drug conjugates for both enfortumab vedotin and sacituzumab govitecan against Trop-2 and looking at those agents earlier in the first-line setting. Why not look at them at the perioperative setting, like neoadjuvant and adjuvant settings? I agree. It’s the most exciting class of agents in the field, with many differences.

I will also raise a couple of other points. No. 1 is that there are other antibody-drug conjugates against Trop-2 that are being developed. Obviously sacituzumab govitecan is safely approved and leads that class. There’s also the issue of variant histologies. It’s important to tackle the issue of managing variant bladder cancer histologies. We talked about urothelial carcinoma, the most common type of bladder cancer, and can also arise from upper tract or urethra. But sometimes we see variant histologies like squamous cell, adenocarcinoma, plasmacytoid, and micropapillary. We try to figure out. Maybe we have to look at the expression of those targets, Nectin-4 and Trop-2—some early data exist—and see if we can utilize antibody-drug conjugates to address the issue of variant histologies.

The other point I want to make is that combinations are probably coming, along with biomarkers. I see the future with more combinations and, hopefully, more biomarkers to help us select the patients for the right treatment. It’s super exciting to see these antibody-drug conjugates—enfortumab vedotin and sacituzumab govitecan—being approved.

With that, I’d like to thank you for all the work you’ve done in the field. This discussion has been extremely informative. Thank you for this insightful discussion. Thanks to the audience for watching this Targeted Oncology™ presentation of “Targeting Trop-2 in Advanced Urothelial Carcinoma.” We hope you found this discussion across the spectrum of urothelial cancer useful. Thanks, Neeraj, for your time.

Transcript edited for clarity.