Targeting FGFR Mutations in Metastatic Urothelial Cancer - Episode 7
Drs Arlene O. Siefker-Radtke and Scott T. Tagawa explain how they would establish goals of therapy and a treatment algorithm for a patient who presents with metastatic urothelial cancer.
Arlene O. Siefker-Radtke, MD: We have a lot of great panels that are available to us. I’m hearing loud and clear from Scott, “Mutation testing from the panel.” Not just for FGFR3, where we have an FDA-approved therapy, but we have other clinical trials using other targets, other mutations. HER2 [human epidermal growth factor receptor 2] expression may become relevant in the future. We see tumor mutational burden as a potential selection for PD-L1 and PD-L1 expression levels, although they’ve never been quite as satisfying. Don’t forget those germline mutations, looking for familial syndromes—things like BRCA mutations or Lynch syndrome, which can occur in upper-tract tumors as well. We’ve got a lot of great panels. Test early. I’m even hearing, “Test often. Try to get biopsies of metastatic sites whenever it’s potentially feasible.” I’d like to move on and present a couple of cases that may help understand our role for use of different biomarker testing in the treatment of patients with urothelial cancer. Ready for me to give you a case and then quiz you on it, Scott?
Scott T. Tagawa, MD, MS, FACP: Go for it.
Arlene O. Siefker-Radtke, MD: The first patient is a 62-year-old man who’s presented to you from their local urologist. He had some dizziness associated with hematuria. He has a history of hypertension, eczema, diverticulitis. He is a former smoker and drinks a few alcoholic beverages each week. Unfortunately, on imaging studies, he’s found to have not only a large bladder mass but evidence of liver metastases. The urologist who had done a biopsy confirmed a stage IV urothelial carcinoma, and it looks like urothelial carcinoma based on tissue from the bladder. The performance status is 1 with a creatinine clearance of 54 mL/min. Molecular testing showed PD-L1 at 10%, and the patient is positive for an FGFR3 mutation.
What’s your standard approach for first-line therapy for this type of patient, who presents with metastatic urothelial carcinoma?
Scott T. Tagawa, MD, MS, FACP: By way of background, it’s been great to have multiple approvals in this disease; we haven’t for a long time. For me, first-line therapy is still, “Cisplatin, yes or no? Can I get into a patient safely, yes or no?” This sounds like a borderline case. Based on the clearance, let’s leave this case for a minute. This is most important in, say, a clinical T2 or T3, where we’re looking at new adjuvant chemotherapy, and I would do everything we can to improve renal function and get neoadjuvant cisplatin in. That might be followed, depending on what’s leftover with adjuvant immunotherapy, but we’ll ignore that for now.
For metastatic disease, to remind everyone why we think about cisplatin—there’s toxicity, there’s a lot of chair time, and a lot of other practicalities for both the oncologist as well as the patient. When you look at every single cisplatin-based combination trial, there’s a tail of the curve. And the tail of the curve has come back with immunotherapy. But for those who are cisplatin eligible, 10% to 15% will have long-term survival with cisplatin-based chemotherapy. This is before the current era of additional lines of therapy. I would expect less of a chance of that in the setting of liver metastasis. That being said, this patient sounds relatively healthy before.
I would see if there’s any obstructive component to the renal insufficiency. I don’t remember if there were any details about that because of anemia or some other factor. But I’d probably give the patient the benefit of the doubt and see if we could get in, probably in a fractionated way, cisplatin plus gemcitabine—a split dose, some people say, rather than fractionated—and try and get gemcitabine- cisplatin in. If not, then more chemotherapy. I don’t see a reason that the person couldn’t get carboplatin—gemcitabine-carboplatin if that was not available. For both of those, I have in mind avelumab maintenance, assuming that there was at least some disease control.
Transcript edited for clarity.