MHRA positive opinion for avelumab as bladder cancer first-line maintenance treatment

UK Medicines and Healthcare Products Regulatory Agency (MHRA) has issued an Early Access to Medicines Scheme (EAMS) positive scientific opinion for avelumab as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma (UC – bladder cancer) that has not progressed with first-line platinum-containing chemotherapy.

The MHRA issued its positive scientific opinion based on results from the Phase III JAVELIN Bladder 100 study, which was presented earlier this year at ASCO 2020 Virtual Scientific Meeting.

The positive scientific opinion approval is based on results from the Phase III JAVELIN Bladder 100 study, which demonstrated a significant 7.1-month improvement in median OS with avelumab as first-line maintenance plus best supportive care (BSC) compared with BSC alone: 21.4 months (95% CI: 18.9 to 26.1) vs. 14.3 months (95% CI: 12.9 to 17.9).1,2

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 to 0.86; 2-sided P=0.001).2 OS was measured from the time of randomisation, after patients were treated with four to six cycles of gemcitabine plus cisplatin or carboplatin over a period of approximately four months.2 The JAVELIN Bladder 100 interim analysis results were presented at the ASCO 2020 Virtual Scientific Meeting.3

Platinum-based chemotherapy is currently the first-line standard of care for eligible patients with advanced disease based on high initial response rates. However, most patients will ultimately experience disease progression within nine months of initiation of treatment4,5 and only 5% of patients with metastatic disease will live longer than five years.6

Dr Mike England, Medical Director, Merck UK & Ireland said: “Bladder cancer is the eleventh most common cancer in the UK, with urothelial carcinoma being the most common type of bladder cancer, accounting for 90 percent of all cases. However, treatment options are limited and survival rates are poor. Therefore, we are delighted by the MHRA’s positive decision to provide early access to avelumab, as there is a significant unmet need in this therapy area for new treatment options for these patients. We believe this is a major advance in the existing standard of care and will improve patient outcomes.”

Dr Olivia Ashman, Oncology Medical Director, Pfizer UK said: “Avelumab is the first immunotherapy to demonstrate in a clinical trial a statistically significant improvement in overall survival as a first-line treatment for patients with advanced urothelial carcinoma. It is our greatest hope that our maintenance approach can eventually become part of routine clinical practice and significantly prolong survival for these patients.”

Avelumab is not licensed in the UK for locally advanced or metastatic urothelial carcinoma and a marketing authorisation application for this indication is currently under review by the European Medicines Agency (EMA).


  1. Early Access to Medicines Scientific Opinion – Public Assessment Report – Avelumab (EAMS number 11648/0003) Available at: Accessed September 2020.
  2. Pfizer Inc. Interim Clinical Study Report: JAVELIN Bladder 100/B9991001, 2020.
  3. Powles T, et al. “Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma: JAVELIN Bladder 100 phase III results.” 2020 ASCO Annual Meeting, 31 May 2020, oral presentation (virtual) Abstract LBA1. Conference Presentation.
  4. Bukhari N, et al. Update on the treatment of metastatic urothelial carcinoma. Scientific World Journal. 2018;2018:5682078.
  5. Von der Maase H, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. Journal of Clinical Oncology. 2005;23(21):4602-4608.
  6. Queen’s University Belfast. Cancer incidence, prevalence and survival statistics for Northern Ireland: 1993-2017. Bladder cancer (C67), 2019.