Frontline Therapy for Advanced Urothelial Carcinoma
Robert Dreicer, MD, MS, MACP, FASCO: In this case, we have a woman in her mid-60s who presents with de novo metastatic disease. The TURBT [transurethral resection of bladder tumor] establishes the fact that she has invasive urothelial cancer, and the CT scans are consistent with metastatic disease.
As we would do for all comers with metastatic urothelial cancer, we would basically tell this patient that if she’s able to receive cisplatin-based chemotherapy—her creatinine clearance and her performance status would suggest that she could—we would typically say that her survival is in the range of 13 to 15 months based on level 1 evidence from older and newer trials.
For the decision about frontline treatment and some of the other factors that go into it, in the current paradigm we’re still using platinum-based therapy. We decide between cisplatin- and carboplatin-based therapy. There’s compelling evidence that cisplatin-based chemotherapy has the potential in a small subset of patients—perhaps 5% to 15% of patients—primarily those with nodal disease. This patient may have lung metastases, although that’s not clear, but she has clear nodal metastases. This patient has an ECOG performance status of 1 and a creatinine clearance in the mid-60s mL/min. Therefore, if I could administer it, I would offer cisplatin-based therapy.
Obviously there are certain factors that are relatively well established that would suggest cisplatin ineligibility, and that would include patients with creatinine clearances less than 60 mL/min, patients who have ECOG performance statuses of 2 or worse, and patients who may have very significant preexisting neuropathy and hearing disorders, although those are lesser-type issues. It really comes down to renal function and performance status.
One of the questions that arises now is, do we do next-generation sequencing given the fact that downstream there are drugs approved for patients with specific FGFR2 and FGFR3 mutations?
The timing of that is not absolutely established. Obviously, if she was going to go on a clinical trial that might be part of it. You have the tissue, so you could certainly do the testing at this point. It wouldn’t change what I do now, but I would certainly want that information. Whether I test it now or ensure that the tissue is available for subsequent use if in fact the patient requires additional therapy, I would want that in the bank.
In this patient, we’ve assessed the fact that the patient is a candidate for chemotherapy based on her performance status and renal function, and we would use cisplatin. Questions arise, perhaps not in this patient but in other patients who may be either equivocal for cisplatin-based therapy or not candidates, such as, what’s the role of PD-L1 testing on tissue?
We have FDA guidance that recommends that although 2 drugs—atezolizumab and pembrolizumab—were approved in non–cisplatin-eligible patients, it requires PD-L1–positive expression. In that setting, I would certainly send PD-L1 testing. At this point, for patients who have cisplatin-eligible disease, PD-L1 testing doesn’t inform my decision. Therefore, I probably would not do that at this point.
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
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