Checkpoint Inhibitors for Advanced Urothelial Carcinoma
Robert Dreicer, MD, MS, MACP, FASCO: Following the presentation of JAVELIN Bladder 100, many of us who manage this disease frequently were obviously very impressed. This is really a quite significant improvement in survival, and it alters how I manage my patients. Today, when I see patients who are receiving cisplatin-based chemotherapy up front or even carboplatin, I’m counseling them up front. I say, “Here are the data that we have, and if we achieve this kind of level of response…”
Basically, for anybody who does not progress through frontline therapy, I’m already counseling them about the potential use of avelumab based on JAVELIN Bladder 100. That has now become a standard of care when managing these patients.
Of course, issues arise about the potential to treat everybody who has stable disease or better vs some patients, for example, who achieve CRs [complete responses] or high-grade PRs [partial responses], especially patients who may be cured with chemotherapy and therefore do not relapse and could potentially be overtreated.
These are some of the issues we’re going to have to come to grips with. For patients with stable disease, certainly I would essentially offer avelumab. Based on the outcomes of patients with stable disease—this disease is relatively poor—I would be very anxious to add that therapy on as switch maintenance.
It’s going to take a bit of clinical judgment, certainly with CRs with nodal disease or PRs with nonvisceral crisis metastatic disease, when making decisions about whether the timing is right for switch maintenance or second-line therapy is more apt.
Those are unknowns, but those are the kinds of conversations we’re going to have to have with our patients. It’s altered my clinical practice as of the day I saw the data. Obviously, we waited for the drug’s approval. But now that this is a standard of care, we need to have this conversation with all our patients in this clinical setting.
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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