Advanced Urothelial Carcinoma: First-Line Maintenance

EP: 1.Case Review: 65-Year-Old Female With Urothelial Carcinoma

EP: 2.Frontline Therapy for Advanced Urothelial Carcinoma

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EP: 3.Advanced Urothelial Carcinoma: First-Line Maintenance

EP: 4.Avelumab for Advanced Urothelial Carcinoma: Safety Profile

EP: 5.Checkpoint Inhibitors for Advanced Urothelial Carcinoma

EP: 6.Progress in Advanced Urothelial Carcinoma

Robert Dreicer, MD, MS, MACP, FASCO: Because this patient has obtained at least stable disease based on CT imaging—resolution or disappearance or just not visualization of the small pulmonary nodules, a decrease in the bladder mass, and at least stable disease in the nodes—she would be a candidate for avelumab based on JAVELIN Bladder 100.

Given the compelling data that we’ll talk about in a bit more detail, I would initiate cisplatin-based chemotherapy with the hope that we could obtain a high-grade PR [partial response] or CR [complete response], but understanding that even in stable disease we would be thinking ahead about the role of avelumab. I would inform the patient that this is part of the management strategy, and that we would evaluate once we complete the chemotherapy or get a best response.

Avelumab has recently received FDA approval for switch maintenance based on the JAVELIN Bladder 100 study. That was a very well done, large randomized trial that compared patients who achieved stable disease or better receiving at least 4 cycles of platinum-based chemotherapy and randomized them to receive switch maintenance with avelumab or best standard of care.

That study was presented at ASCO [American Society of Clinical Oncology Annual Meeting] in the plenary session and showed a very significant survival advantage favoring avelumab switch maintenance. The overall survival in the all-comers population was 21 months compared with best supportive care—about 14 months. The 14-month survival seen in the platinum-based chemotherapy arm is consistent with historical numbers; therefore, it is a very good representation in the control arm. Obviously, the survival in the avelumab arm was highly statistically significant.

Additionally, they looked at PD-L1–positive-expressing patients. Although the control arm had a median OS [overall survival] of 17 months, that has not been reached—the overall survival rate in the avelumab arm. This establishes, in my mind, avelumab as a standard of care in patients achieving stable disease or better based on a compelling level of improvement in overall survival.

There are issues related to toxicity, but first let’s touch on progression-free survival, which also favored the avelumab arm in the overall population. There, the number was 3.7 months vs 2 months. In the PD-L1–positive group, 5.7 vs 2.1 months.

Avelumab has some potential infusion reactions that are typically seen in cycles 1 through 4, and that was also observed here. Adverse events are consistent with checkpoint inhibitor use in the frontline and second-line settings of advanced urothelial cancer.

Based on the way this patient presented—achieving at least stable disease with platinum-based chemotherapy—the decision was made to use avelumab based on JAVELIN Bladder 100 and its compelling data.

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