Progress in Advanced Urothelial Carcinoma
Robert Dreicer, MD, MS, MACP, FASCO: Advanced urothelial cancer, after decades of really no progress at all, has exploded like a lot of other areas in oncology. All we had for 25 or 30 years was platinum-based chemotherapy. We’ve seen multiple checkpoint inhibitors approved that have impacted the natural history of the disease, and some have dramatically changed what happens to people. Again, the challenge with checkpoint inhibitors is they still only impact 1 of 5 patients. But all of us who manage this disease have patients who are multiple years out. They may not be cured, but they also may not die of urothelial cancer. So progress has been made.
Recent approvals of erdafitinib for FGFR2- and FGFR3-mutated patients, and enfortumab vedotin, have been badly needed for second- and third-line therapy.
There have been some setbacks with the frontline trials of checkpoint inhibitors plus chemotherapy. The adjuvant study of atezolizumab was also negative. But there are a lot of exciting combinations in the pipeline. There are some very intriguing data on the combination of enfortumab vedotin with pembrolizumab. We’ve seen that data, in terms of phase 2 experiences.
We’ve also seen other checkpoint inhibitor approvals: Pembrolizumab for BCG [Bacillus Calmette-Guerin]–unresponsive, high-grade, T1 nonmuscle-invasive disease with carcinoma in situ. That’s also very exciting.
There are very compelling data on the use of checkpoint inhibitors in the neoadjuvant setting. There are a range of studies, including enfortumab plus checkpoint novel FGFR agents that are moving into the neoadjuvant setting. Upper-tract disease highly enriched with FGFR mutations. Also, FGFR agents moving into those settings.
So this is a really exciting time in urothelial cancer. There are a lot of trials, including another CTLA4-plus-checkpoint-inhibitor study. We know of the enfortumab up-front trials. This is a very intriguing time. There are lots of moving parts. There is probably no defined sequence right now. There are multiple sequences we can use. Although we’d like to have definitive data about everything, we have multiple agents moving in with new combinations that are going to be reporting. It’s a pretty exciting time for those of us who manage this disease state.
Transcript edited for clarity.
Case: A 65-Year-Old Female With Urothelial Carcinoma
Initial presentation
- A 65-year-old female presents with 2 weeks of intermittent gross hematuria
- PMH: COPD, HTN
- SH: 30-pack year smoking history
Clinical workup
- Labs: Hb 10.2 g/dl, WBC 2.8 x 109/L, creatinine 1.3 mg/dL, creatinine clearance 68 ml/min; other WNL
- TURBT large bladder mass, high grade muscle invasive urothelial cancer
- CT scan of the abdomen and pelvis: large bladder mass, pelvic and para aortic adenopathy (largest 2.2 cm); CT Chest 3 sub cm nodules uncertain significance
- Stage T3N2M1
Treatment
- The patient received cisplatin + gemcitabine for 6 cycles; stable disease
- Repeat imaging CT chest 2 of the sub cm lesions no longer appreciated
- CT abd/pelvis decrease size in bladder mass, nodal findings mildly improved, no new disease
- Avelumab 10 mg/kg IV q2W was started 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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