FDA Approves Avelumab as Frontline Maintenance in Metastatic Urothelial Carcinoma


The FDA has approved avelumab (Bavencio) as maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-based chemotherapy.1

The regulatory decision is based on data from the pivotal phase 3 JAVELIN Bladder 100 study, which showed a significant improvement in median overall survival (OS) of 7.1 months with avelumab as frontline maintenance treatment plus best supportive care (BSC) versus BSC alone.

“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 one of the most significant advances in the treatment paradigm in this setting in 30 years,” Petros Grivas, MD, PhD, one of the principal investigators of the JAVELIN Bladder 100 trial said in a recent press release.

“With median OS of more than 21 months measured from randomization, the longest OS 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,” added Grivas.

Results from the trial were presented during the 2020 ASCO Virtual Scientific Program and showed a median OS of 21.4 months with avelumab (95% CI, 18.9-26.1) versus 14.3 months with BSC alone (95% CI, 12.9-17.9); this translated to a 31% reduction in the risk of death in the overall patient population (hazard ratio [HR], 0.69; 95% CI, 0.56-0.86; 2-sided P =.001).2,3

Notably, the benefit with avelumab extended across all prespecified subgroups, including those defined by cisplatin-based or carboplatin-based chemotherapy, and regardless of whether response or stable disease was reached after frontline induction chemotherapy.

In the multicenter, international, open-label, parallel-arm, randomized phase 3 trial, investigators examined frontline avelumab maintenance therapy in combination with BSC (n = 350) compared with BSC alone (n = 350) in a total of 700 participants with unresectable locally advanced or metastatic urothelial cancer whose disease did not progress on 4 to 6 cycles of standard gemcitabine paired with either cisplatin or carboplatin.

Patients enrolled on the trial had experienced a complete response, a partial response, or stable disease with chemotherapy. They received treatment between 4 to 10 weeks post induction chemotherapy. Just more than half of patients, or 51%, had tumors with PD-L1 positivity.

Avelumab was given intravenously at 10 mg/kg every 2 weeks in 4-week treatment cycles. BSC included antibiotics, nutritional support, correction of metabolic disorders, as well as symptom control and pain management.

The co-primary end points of the trial were OS in all randomized patients as well as in those with PD-L1—positive tumors. Secondary endpoints of the trial were comprised of progression-free survival (PFS), antitumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers, and patient-reported outcomes in the co-primary patient populations.

The median follow-up was 19.6 months in the avelumab arm and 19.2 months in the BSC-alone arm. Additional results demonstrated that in the cohort of patients with PD-L1—positive tumors, the median OS had not yet been reached in those who received avelumab versus 17.1 months in those who received BSC alone (HR, 0.56; 95% CI, 0.40-0.79; P = .0003).

In the overall patient population, the median PFS was 3.7 months in the avelumab-plus-BSC arm compared with 3.7 months in the BSC-alone arm per blinded independent central review (HR, 0.62; 95% CI, 0.52-0.75; P <.001). Additionally, the HR for PFS favored avelumab in the PD-L1—positive subgroup, as well (HR, 0.56; 95% CI, 0.43-0.73).

With regard to safety, investigators examined a total of 344 patients in the avelumab arm and 345 patients in the BSC-alone arm and found avelumab to be very well tolerated. All-grade, any-cause adverse events (AEs) were reported in 95% of those who received avelumab versus 77.7% of those who received the control. Grade 3/4 AEs were experienced by 47.4% and 25.2% of those in the avelumab/BSC and BSC-alone arms, respectively. The most common grade ≥3 AEs reported in the avelumab and control arms included urinary tract infection (4.4% vs 2.6%, respectively), 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%).

Previously, in 2017, avelumab was granted an accelerated approval from the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience 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.


FDA approves Bavencio as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. News release. Pfizer. June 30, 2020. Accessed June 30, 2020. bit.ly/2YO7gVk.

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. J Clin Oncol. 2020;38(suppl 18):LBA1. doi:10.1200/JCO.2020.38.18_suppl.LBA1.

Immunotherapy Following Chemotherapy Offers Extended Survival to Patients with Advanced Urothelial Cancer. News release. ASCO. May 28, 2020. Accessed June 30, 2020. bit.ly/2TO5SPz.

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