Results of the JAVELIN Bladder 100 Trial


Neeraj Agarwal, MD: Obviously, the standard of care for first-line therapy has changed, and it changed during ASCO [American Society of Clinical Oncology Annual Meeting] in 2020. What really changed? The data from the JAVELIN Bladder 100 trial showed that avelumab, a PD-L1 inhibitor, was associated with a dramatic improvement in overall survival. This was the case when avelumab was started after completion of 4 to 6 cycles of chemotherapy, whether it was cisplatin- or carboplatin-based chemotherapy, and if the patient did not have disease progression. They were either responding or had stable disease and were able to finish 4 to 6 cycles of carboplatin and gemcitabine or cisplatin and gemcitabine.

The frontline maintenance therapy with avelumab approach was approved by the FDA within weeks of the data being presented at ASCO. Almost at the same time, all the guidelines, whether they were national guidelines in the United States, such as the NCCN [National Comprehensive Cancer Network] Guidelines, or were European guidelines, ESMO [Clinical Practice] Guidelines, incorporated avelumab as the category 1 treatment, or the preferred treatment option for these patients.

Let’s talk about the data from the JAVELIN Bladder 100 trial, which was presented at ASCO 2020. In this study, 700 patients with locally advanced unresectable or metastatic urothelial carcinoma who had stable disease or a partial response after 4 to 6 cycles of platinum-based chemotherapy were randomized to receive frontline maintenance therapy with avelumab plus best supportive care, vs best supportive care alone. For patients who received best supportive care alone, there were periodic scans and follow-up but with no active intervention.

These patients were randomized to receive frontline maintenance therapy with avelumab vs best supportive care. The primary end point was overall survival. Secondary end points looked at progression-free survival and responses.

Results were really dramatic. I don’t think we have ever seen this magnitude of survival benefit in the context of patients with metastatic urothelial carcinoma receiving treatment with immune checkpoint inhibitors. In patients who were randomized to the avelumab arm, the median survival was approximately 21 months. In patients randomized to best supportive care, the overall survival was 14 months, approximately. So there was a 7-month absolute improvement in overall survival. If we look at the hazard ratio for increase in survival, it is 0.69. We see almost a 30% reduction in risk of death by employing frontline maintenance therapy with avelumab.

If you look at the PD-L1–positive population in a predefined subset analysis, the hazard ratio for improved overall survival was 0.56. So it was very pronounced. Having said that, it doesn’t take away any positivity from the overall survival benefit seen across the population in the JAVELIN Bladder 100 trial. Overall, the hazard ratio for improvement in survival was 0.69, and that was for all patients, regardless of PD-L1 expression in the tumors.

Regarding overall survival, the gold standard was remarkably positive in patients receiving treatment with avelumab. But if you look at the secondary end points, progression-free survival was also improved on treatment with avelumab.

Response rates are really not a very nice way to look at the benefit with avelumab in this patient population. If you recall, these patients had to be responding or have stable disease on treatment with platinum-based chemotherapy. This patient population consists of people who either are responding to platinum-based chemotherapy or had stable disease. They did not have progressive disease at the time of entry. So the objective responses, although better with avelumab, don’t have much clinical relevance. It’s overall survival that really drives my clinical decision as I look at these data.

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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