Avelumab Approved by FDA for the Treatment of Locally Advanced Urothelial Carcinoma

The FDA approved avelumab as a frontline maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma who have not progressed with frontline platinum-based chemotherapy.

The FDA has granted approval to avelumab (Bavencio) as a frontline maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma who have not progressed with frontline platinum-based chemotherapy.1

This is the first and only immunotherapeutic option approved by the FDA that has demonstrated significant overall survival (OS) benefit in the frontline setting in a phase 3 trial. In the JAVELIN Bladder 100 study, avelumab maintenance extended OS by 50% compared with the standard of care.

“As the first immunotherapy to demonstrate a statistically significant improvement in OS in the first-line setting in locally advanced or metastatic urothelial carcinoma, the FDA approval of avelumab is 1 of the most significant advances in the treatment paradigm in this setting in 30 years,” said Petros Grivas, MD, PhD, 1 of the principal investigators in the JAVELIN Bladder 100 trial, in a statement. Grivas is director of the Genitourinary Cancers Program at UW Medicine. “With median overall survival of more than 21 months measured from randomization, the longest overall survival in a phase 3 trial in advanced urothelial carcinoma, the JAVELIN Bladder 100 regimen with avelumab as a first-line switch maintenance treatment has the potential to become a new standard of care based on its proven ability to reinforce the benefit (response or stable disease) of induction chemotherapy and extend the lives of patients with this devastating disease.”

The approval was based on these positive findings from the phase 3 JAVELIN Bladder 100 study, which were recently presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program. The trial demonstrated a 7.1-month improvement in the median OS with frontline avelumab maintenance combined with best supportive care (BSC) compared with BSC alone.2

The median OS was 21.4 months with avelumab (95% CI, 19.9-26.1) versus 14.3 months with BSC alone (95% CI, 12.9-17.9), and this was a statistically significant improvement, demonstrating a 31% reduction in the risk of death in the overall population (HR, 0.69; 95% CI, 0.56-0.86; 2-sided P = .001).

In the multicenter, international, open-label, parallel-arm JAVELIN Bladder 100 study, 700 patients with unresectable locally advanced or metastatic urothelial cancer were randomized to receive either avelumab plus BSC (n = 350) or BSC alone (n = 350). Patients had to have received 4 to 6 cycles prior cycles of standard gemcitabine with either cisplatin or carboplatin and achieve a complete response, partial response, or stable disease. Patients received their treatment between 4 and 10 weeks after induction chemotherapy. Overall, 51% (n = 358) of the patients had tumors that were PD-L1 positive.

The median follow-up was 19.6 months in the avelumab arm and 19.2 months in the control arm. Among patients with PD-L1–positive tumors, the median OS had not yet been reached in the avelumab arm compared with 17.1 months in the control arm (HR, 0.56; 95% CI, 0.40-0.79; P = .0003).

The median progression-free survival (PFS) per blinded independent central review in the overall population was 3.7 months with avelumab versus 2 months without (HR, 0.62; 95% CI, 0.52-0.75; P <.001). The HR for PFS also favored the avelumab arm in the PD-L1–positive group (HR, 0.56; 95% CI, 0.43-0.73).

All-grade “any-cause” adverse events (AEs) occurred in 98% of patients in the avelumab arm versus 77.7% in the control, and grade 3/4 AEs occurred in 47.4% versus 25.2%, respectively. The most common grade 3 or greater AEs in the avelumab versus control arms included urinary tract infection (4.4% vs 2.6%), anemia (3.8% vs 2.9%), hematuria (1.7% vs 1.4%), fatigue (1.7% vs 0.6%), and back pain (1.2% vs 2.3%), respectively.

Avelumab was administered to patients intravenously at 10 mg/kg every 2 weeks in 4-week cycles. BSC could include antibiotics, nutritional supportive, correction of metabolic disorders, and symptom control and pain management.

The current standard of care in the frontline setting for this patient population is platinum-based chemotherapy. However, most patients will progress within 9 months of initiation of treatment, and only 5% with metastatic disease will live longer than 5 years. For patients who do not progress following treatment with platinum-based chemotherapy, avelumab is administered as a frontline maintenance therapy until either disease progression or unacceptable toxicity occur.1

Avelumab is also FDA approved for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. The JAVELIN Bladder 100 trial served as confirmation for the continued approval of avelumab in this setting. The FDA has therefore converted the accelerated approval to a full approval.


  1. FDA approves Bavencio as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. News Release. Pfizer. June 30, 2020. Accessed July 1, 2020. https://bit.ly/2D29eJv
  2. Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. Presented at: 2020 ASCO Virtual Scientific Program; May 29-31, 2020. Abstract LBA1.