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Penpulimab Plus Anlotinib Evaluated for Previously Treated Urothelial Cancers


Dr Siefker-Radtke provides her closing thoughts on her takeaways from ESMO 2022, including a study focusing on penpulimab plus anlotinib.

Arlene Siefker-Radtke, MD: Another interesting abstract at this year’s ESMO [European Society for Medical Oncology Congress] is the combination of penpulimab plus anlotinib. Penpulimab is another checkpoint inhibitor. In this case, it comes from China. [It’s combined] with anlotinib, which is a tyrosine kinase inhibitor [TKI]. The tyrosine kinase inhibitor anlotinib targets multiple tyrosine kinases, a lot of which associated with the VEGF pathway, and it has PDGF and FGF inhibition. It targets multiple pathways in the tyrosine kinase kinome.

We saw early data presented from a trial exclusively in China that enrolled 15 patients. It’s a very small clinical trial, which is one limitation of the data that have been presented so far. The response rate appears promising, with an objective response rate of around 33%. But that means 5 out of 15 patients. We still have a very significant limitation with small numbers. It also doesn’t tell us the contribution of components. How much of this activity is from the immune checkpoint inhibitor? How much of the activity is from the tyrosine kinase inhibitor?

In looking at the data from the trial, we see a significant number of patients with node-only metastases. We have to keep in mind that in the setting of node-only disease, response rates with immune checkpoint inhibitors are higher compared with what’s observed in the setting of liver metastases, where the response rates are rather low. Additional information that I’d like to see includes: where are these responders? Are the responders only in the node-only cohort? Are there more responses in the visceral metastases cohort? It would certainly be exciting if we saw a large number of liver metastases responding as well.

Given the multifocal targets associated with anlotinib, it’s also important to find out whether these patients have FGF mutations. It’s possible that through patient selection, there’s enrichment for a cohort of patients who are able to be targeted by this tyrosine kinase. This combination is showing promise, and there’s clear clinical activity, but more data are needed to assess the contribution of each component and whether there’s any potential for selection bias that might be accounting for the improved response rate that has been seen thus far. I look forward to seeing more patients enrolled on this combination and more data coming out to help us understand how much benefit we may achieve with this potentially promising combination of a TKI, anlotinib, with an immune checkpoint inhibitor, penpulimab.

When summarizing where the field is moving in urothelial cancer, I have to admit these targeted strategies are showing significant promise in enhancing the clinical outcomes for our patients with bladder cancer in general. We’ve seen personalized agents targeting FGFR3 with the approval of erdafitinib [Balversa]. We’ve also seen other ways of targeting tumors by bringing these very toxic chemotherapy strategies more directly to the tumor or tumor microenvironment by targeting nectin-4 with enfortumab vedotin [Padcev], targeting Trop-2 with sacituzumab govitecan [Trodelvy], and now a potential HER2-targeting strategy as well. There are a lot of other TKIs showing promise, and which ones will be around tomorrow depends on the results of trials that are accruing today.

We’re heading into personalized therapy for our patients with urothelial cancer. We’ll learn how to target these tumor cells more directly, enhance cell kill in the tumor microenvironment, and turn on a better immune response that can generate longer and more durable responses in general. There are very high hopes that someday we might send chemotherapy to the leeches and think of cisplatin as something we used to do in the past that may not be part of the future. But we need more data. We need these trials to accrue. I encourage everyone to send their patients for all of these very promising clinical trials in urothelial cancer as we head toward more personalized therapy, enhancing patient overall survival.

Transcript edited for clarity.

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