NICE Makes Avelumab Available for Maintenance Treatment of Urothelial Cancer

Avelumab (Bavencio) is now a treatment option for patients with urothelial cancer (UC) in the United Kingdom following a recommendation from the National Institute for Health and Care Excellence (NICE) issued Thursday, April 7, 2022.¹

The anti­–PD-L1 monoclonal antibody is approved for routine coverage under the National Health Service (NHS). Avelumab is indicated as maintenance therapy for adults with locally advanced or metastatic UC that has not progressed following platinum-cased chemotherapy. As a condition of the approval, avelumab must be stopped at 5 years of uninterrupted treatment, or earlier if there is disease progression.

“[Individuals] with locally advanced or metastatic UC often have poor quality of life and poor prognosis,” Helen Knight, interim director for medicines evaluation at NICE, said in a news release. “Avelumab is a promising drug which has the potential to extend life. The committee recognized there are few treatments available to people with this form of cancer, many of whom have to wait until their disease gets worse before they are able to have immunotherapy or further courses of chemotherapy.”

The announcement reverses a NICE decision made in May 2021 rejecting the use of avelumab in this patient population.² At the time, NICE appraisers concluded that avelumab extended progression-free survival (PFS) and overall survival (OS) compared with the best supportive care (BSC). However, they decided that cost-effectiveness estimates were significantly higher than NICE considers an acceptable use of NHS resources. Furthermore, because there were no planned or ongoing studies addressing the key uncertainties in the evidence provided at the time, NICE ruled that avelumab did not meet the criteria for inclusion in the Cancer Drugs Fund.

Merck Serono filed an appeal with NICE in September 2021, arguing that the ruling was inconsistent with previous decisions on other immunotherapy agents.

The new NICE decision is based on findings from the phase 3 JAVELIN Bladder 100 trial (NCT02603432), in which investigators examined frontline avelumab maintenance therapy in combination with BSC (n = 350) compared with BSC alone (n = 350). Eligible patients had experienced a complete response, a partial response, or stable disease with chemotherapy.

Investigators administered 10 mg/kg avelumab was given intravenously at 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.

With an additional 19 months of follow-up, the median OS with avelumab plus BSC was 23.8 months (95% CI, 19.9-28.8) compared with 15.0 months (95% CI, 13.5-18.2) with BSC alone (HR, 0.76; 95% CI, 0.631-0.915; P = .0036). OS rates at 2 and 3 years with avelumab/BSC were 49.8% and 36.0%, respectively; these rates were 38.4% and 29.8%, respectively, in the BSC-alone arm.⁴

The investigator-assessed PFS was 5.5 months (95% CI, 4.2-7.2) with avelumab/BSC and 2.1 months (95% CI, 1.9-3.0) with BSC alone (HR, 0.54; 95% CI, 0.457-0.645; P <.0001). PFS rates at 2 and 3 years were 23.4% and 15.9%, respectively, with avelumab/BSC, and 7.1% and 5.3%, respectively, with BSC alone.

The FDA in June 2020 approved avelumab based on previous JAVELIN Bladder 100 results.⁵ In those data, 1-year OS was 71.3% in the avelumab group vs 58.4% in the control group. The median OS also favored the experimental arm 21.4 vs 14.3 months (HR for death, 0.69; 95% CI 0.56-0.86; P = .001). The median PFS was 3.7 months in the avelumab group compared with 2.0 months in the control group (HR, 0.62; 95% CI, 0.52-0.75).⁵

Drug makers Pfizer and Merck KGaA agreed to provide avelumab to the NHS at a discount, the size of which was not disclosed. At present, the drug costs £768.00 or $997.97 per 200 mg/10 mL vial.⁶

References

1. National Institute for Health and Care Excellence. Hundreds of people with some forms of urothelial cancer to receive new treatment. News release. Published April 7, 2022. Accessed April 8, 2022. bit.ly/3Kq24wm
2. National Institute for Health and Care Excellence. Avelumab not recommended as a maintenance treatment of urothelial cancer after platinum-based chemotherapy. News release. Published May 7, 2021. Accessed April 8, 2022. bit.ly/3xd7qHr
3. Powles T, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): long-term follow-up results from the JAVELIN Bladder 100 trial. J Clin Oncol. 2022;40(suppl 6):487. doi:10.1200/JCO.2022.40.6_suppl.487
4. FDA approves Bavencio as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. News release. Pfizer. June 30, 2020. Accessed April 8, 2022. bit.ly/2YO7gVk
5. Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020;383(13):1218-1230. doi:10.1056/NEJMoa2002788
6. National Institute for Health and Care Excellence. Avelumab for maintenance treatment of locally advanced or metastatic urothelial cancer after platinum-based chemotherapy—final appraisal document. Published April 7, 2022. Accessed April 8, 2022. https://bit.ly/38Dv5qj