Future Directions for Treating Urothelial Carcinoma
Neeraj Agarwal, MD: We have seen exciting advances in the treatment of metastatic or locally advanced urothelial carcinoma. We saw the approval of 5 PD-1 axis inhibitors over the last 3 years in the second-line urothelial carcinoma setting, after disease progression following platinum-based chemotherapy. Then we saw avelumab get approved as frontline maintenance therapy, which dramatically improved the overall survival benefit. We also saw antibody-drug conjugates, or the conjugate enfortumab, garner FDA approval for patients who have had disease progression on earlier lines of therapies in metastatic urothelial carcinoma. In addition, we saw erdafitinib, a FGFR pathway inhibitor, become available for patients who have had disease progression on earlier lines of therapies and are harboring FGFR alterations and fusions. All this is just a start, in my opinion. We are going to be seeing more antibody-drug conjugates get approved. In my view, the data presented on sacituzumab, another antibody-drug conjugate, are very promising. Hopefully we’ll see this agent become available for patients with advanced urothelial carcinoma.
We are seeing combinations of immune checkpoint inhibitors with antibody-drug conjugates moving to frontline therapy in clinical trials. Overall, this is very exciting news for us, for our patients, and hopefully we will not have to tell our patients that the median survival is only 18 months when they see us with a diagnosis of metastatic urothelial carcinoma in the future. Hopefully we’ll keep them alive with good quality of life for years. We are only a few years away from that happening.
Transcript edited for clarity.
Case Overview: A 73-Year-Old Male With Urothelial Carcinoma
Initial presentation
- A 73-year-old man presents with LUTS with intermittent hematuria
- PMH: HTN, well-controlled on an ARB; mild hepatic and renal impairment
- PE: distension of bladder; slow flow on voiding
Clinical workup
- Labs: Hb 11.4 g/dl, WBC 3.5 x 109/L, AST and ALT: ~4x ULN, CrCl: 35 mL/min; others WNL
- Cystoscopy: showed a 2.6 cm mass around the neck of the bladder
- TURBT was performed; transition cell carcinoma of the urothelium, with tumor invading the perivesical tissue
- Chest/abdomen/pelvic CT scan: large bladder mass, evidence of multiple regional lymph nodes involved (perivesical and sacral), and a 2.3 cm mass in the left upper lobe
- Stage IIIB; ECOG PS 1
Treatment
- Patient received 6 cycles of carboplatin + gemcitabine; achieved partial response
- CT abdomen/pelvis showed decrease size in bladder mass, nodal findings mildly improved, no evidence of new disease
- Initiated avelumab 10 mg/kg IV q2W as maintenance therapy
Investigational FGFR3-Selective Inhibitor Shows Promise in Urothelial Cancer
October 28th 2024TYRA-300 showed promising safety and preliminary antitumor activity in FGFR3-altered metastatic urothelial cancer, with a 54.5% partial response rate and 100% disease control in the SURF301 trial.
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