Managing Patients on Avelumab for Urothelial Carcinoma


Neeraj Agarwal, MD: Regarding safety and tolerability of avelumab, we have been using PD-1 and PD-L1 inhibitors, PD-1 axis inhibitors, for almost 5 to 6 years now in genitourinary oncology, whether as standard of care or through clinical trials. Most of us have had pretty good experience managing any adverse effects from these drugs.

As we know, 3% to 4% of patients have grade 3/4 autoimmune adverse effects or immune-related adverse events that we all know how to manage by now. Early recognition and patient education are key. Look for colitis, rashes, and hepatitis early on. Frequently monitor patients. Then, early intervention with steroids is recommended whenever we see these adverse effects evolve to grade 3, even if they are persistent grade 2 events. That is really the standard way to treat these patients across all cancer types when they’re being treated with PD-1 axis inhibitors.

One adverse effect that is a little unusual, not very common, is infusion-related reactions with avelumab. This can happen in 15% of patients. Most of the events are grade 1/2. Grade 3 or 4 infusion-related reactions can happen in a small minority of patients. But again, if we monitor them properly up front, these happen mostly during the earlier cycles, during earlier dosing, and the key is to monitor these patients in the infusion room. If they develop grade 1/2 infusion-related reactions, these are easy to manage. If they happen to have grade 3 or 4 infusion-related reactions, that warrants permanent discontinuation of avelumab.

Let’s look at the grade 1 or 2 infusion-related reactions. We have all learned to use acetaminophen, or Tylenol, with Pepcid, famotidine, to manage these patients. Most of these grade 1 or 2 infusion-related reactions can be prevented, in my experience, and patients tolerate the drug very well. Although we rarely see grade 3 or 4 infusion-related reactions, if they do occur that warrants permanent discontinuation of avelumab, which can happen in 1% to 3% of patients. This can happen with other PD-1 axis inhibitors as well. Nothing was dramatically different with avelumab in this trial.

For patients with locally advanced unresectable or metastatic urothelial carcinoma, after the presentation at the ASCO [American Society of Clinical Oncology] 2020 Annual Meeting, frontline maintenance therapy with avelumab is the preferred treatment option in my practice in all patients who are able to finish 4 to 6 cycles of platinum-based chemotherapy and do not have progressive disease. If patients with locally advanced or metastatic urothelial carcinoma are responding or have stable disease after carboplatin- or cisplatin-based chemotherapy, frontline avelumab maintenance therapy is the standard of care. There is no doubt about this.

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


  • 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

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