FDA Approves Avelumab as First-line Maintenance for Patients with Urothelial Carcinoma

The FDA approved avelumab for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

The FDA has approved the supplemental biologics license application (sBLA) for avelumab (Bavencio) for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy, according to Pfizer, the developer of the agent.

“Many patients newly diagnosed with advanced urothelial carcinoma receive benefit from initial chemotherapy, but we still need treatment options that can help patients live longer,” Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network, said in a press release. “We wholeheartedly support the development of new and promising treatments like [avelumab] that can offer patients and their loved ones hope.”

The approval was based on results from the multicenter, multinational, randomized, open-label, parallel-arm, phase 3 JAVELIN Bladder 100 study, which evaluated first-line maintenance treatment with avelumab plus best supportive care (BSV) versus BSC alone in patients with locally advanced or metastatic UC that did not progress with first-line platinum-containing chemotherapy as per RECIST v1.1.

The primary endpoint was overall survival (OS) in the 2 primary populations of all randomized patients and patients with PD-L1 positive tumors defined by the Ventana SP263 assay. Secondary endpoints included progression-free survival (PFS), anti-tumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers, and patient-reported outcomes in the 2 primary populations. All primary and secondary endpoints were measured from the time of randomization, after completion of 4 to 6 cycles of chemotherapy.

Overall, 700 patients were randomly assigned to receive either 10 mg/kg of intravenous infusion avelumab every 2 weeks plus BSC (n = 350) or BSC alone (n = 350). The study demonstrated a significant 7.1-month improvement in median OS with avelumab as first-line maintenance plus BSC (21.4 months; 95% CI, 18.9-26.1) compared with BSC alone (14.3 months; 95% CI, 12.9-17.9). This statistically significant improvement in OS represents a 31% reduction in the risk of death in the overall population (HR 0.69; 95% CI, 0.56-0.86; 2-sided P = 0.001).

“As the first immunotherapy to demonstrate a statistically significant improvement in overall survival in the first-line setting in locally advanced or metastatic urothelial carcinoma, the FDA approval of avelumab is one of the most significant advances in the treatment paradigm in this setting in 30 years,” one of the principle investigators for JAVELIN Bladder 100, Petros Grivas, MD, PhD, board-certified oncologist at the Seattle Cancer Care Alliance (SCCA), director of the University of Washington (UW) School of Medicine’s Genitourinary Cancers Program, and a UW professor of Oncology, said in a press release.

“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,” Grivas continued.

In patients who were PD-L1 positive (n = 358; 51%), the risk of death was reduced by 44% in the avelumab arm versus the control arm (HR 0.56; 95% CI, 0.40-0.79; 2-sided P-value < 0.001). Similar results were also observed across the pre-specified subgroups of complete or partial response versus stable disease to first-line chemotherapy. In an exploratory analysis of patients with PD-L1 negative tumors (n = 271; 39%), the OS hazard ratio was 0.85 (95% CI, 0.62-1.18).

A fatal adverse event (AE) of sepsis occurred in 1 (0.3%) patient receiving avelumab plus BSC. Serious AEs occurred in 28% of patients receiving avelumab plus BSC. Serious AEs in ≥1% of patients included urinary tract infection (including kidney infection, pyelonephritis, and urosepsis) (6.1%), pain (including abdominal, back, bone, flank, extremity, and pelvic pain) (3.2%), acute kidney injury (1.7%), hematuria (1.5%), sepsis (1.2%), and infusion-related reaction (1.2%). The most common AEs observed (≥20%) in patients who received avelumab plus BSC were fatigue, musculoskeletal pain, urinary tract infection, and rash.

Results from the JAVELIN Bladder 100 results were presented at the ASCO 2020 Virtual Scientific Meeting.

Notably, for patients that do not progress on platinum-containing chemotherapy, avelumab is administered as a first-line maintenance treatment until disease progression or unacceptable toxicity.

In 2017, the FDA approved avelumab under accelerated approval 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, based on tumor response rate and duration of response. However, continued approval was contingent upon verification of clinical benefit, which was demonstrated in JAVELIN Bladder 100. The approval has now been converted from accelerated approval to full approval.


FDA APPROVES BAVENCIO AS FIRST-LINE MAINTENANCE TREATMENT FOR PATIENTS WITH LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA [news release]. Rockland, MA and New York. Published June 30, 2020. pfizer.com/news/press-release/press-release-detail/fda-approves-bavencio-first-line-maintenance-treatment. Accessed July 1, 2020.

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