The Scottish Medicines Consortium recommends Merck & Pfizer’s Bavencio® (avelumab) as Monotherapy for First-Line Maintenance Treatment of Locally Advanced or Metastatic Urothelial Carcinoma (Bladder Cancer)

Today Merck and Pfizer announce that the Scottish Medicines Consortium (SMC) has accepted the immunotherapy BAVENCIO^® (avelumab) for use within NHS Scotland as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC), who are progression-free following platinum-based chemotherapy.

This recommendation for avelumab marks the first time a first-line maintenance immunotherapy for patients with locally advanced or metastatic urothelial (bladder) cancer has been approved by the SMC. However, routine use via the NHS or Cancer Drugs Fund in England and Wales is not currently possible following a decision by the National Institute for Health and Care Excellence (NICE) not to recommend this maintenance treatment option. The Merck-Pfizer Alliance has submitted an appeal to NICE on this decision.

Dr Feng-Yi Soh, Consultant Clinical Oncologist at NHS Highland states: “Clinical data demonstrates the positive impact that avelumab plus best supportive care (BSC) may give after platinum-based chemotherapy, particularly on sustaining disease response from chemotherapy, and prolonging overall survival, without a detrimental impact to the patient’s quality of life. Until now, avelumab was only available in Scotland through the Early Access to Medicines Scheme (EAMS)/EAMS extension for first-line maintenance treatment for eligible adult patients with locally advanced or metastatic UC.”

Lydia Makaroff, Chief Executive of Fight Bladder Cancer, adds: "We are delighted to see that this maintenance treatment has been approved by the SMC. This treatment may give bladder cancer patients good quality time and is the biggest change in advanced bladder cancer management we have had in decades. While it is wonderful that this treatment will be available to those people who need it in Scotland, it is deeply disappointing and unfair that NICE has decided that this drug will not be made available to patients with the same diagnosis in England and Wales, resulting in striking inequity of access to treatment within the UK."

UC, which accounts for 90% of bladder cancer cases,¹ has poor survival outcomes, especially for patients with advanced disease.²  In 2018 bladder cancer was the 11th most common type of cancer in Scotland,³ with a 5-year relative survival rate of 44% in patients diagnosed between 2007-2011.⁴

Although first-line platinum-based chemotherapy for locally advanced and metastatic UC has good initial results, durability of response is limited, so the benefits are short-lived and most patients will experience recurrence of disease.^5,6,7,8 Bladder cancer has high recurrence rates⁹ and most patients have disease progression within approximately nine months of initiation of first-line chemotherapy treatment.^5,6,7

Maintenance therapy in the treatment of cancer typically follows an initial round of treatment and is intended to prevent or delay the cancer’s return or slow the growth.¹⁰ There are currently no maintenance treatments routinely available in the UK for locally advanced or metastatic urothelial cancer that has responded to platinum-based chemotherapy.

Dr Mike England, Medical Director, Merck UK & Ireland, says: “We are extremely pleased that the SMC has approved avelumab as a new treatment option for patients with locally advanced and metastatic UC. This is excellent news for patients in Scotland. Unfortunately for patients in England and Wales, NICE has not recommended avelumab for use on the NHS. We are committed to doing everything we can to provide all patients in the UK with equitable access to new medicines and the best possible treatment outcomes, which is why we are appealing NICE’s decision.”

Results from the Phase III JAVELIN Bladder 100 study submitted to the SMC show that avelumab as monotherapy for first-line maintenance treatment in adult patients who are progression-free following platinum-based therapy can sustain and extend the benefits of chemotherapy.¹¹ These interim data from a cut-off date of 21 October 2019 demonstrated a statistically significant 7.1-month improvement in median overall survival (OS) for the whole trial population with avelumab plus best supportive care (BSC) compared with BSC alone (21.4 months (95% Confidence Interval (CI): 18.9 to 26.1) vs. 14.3 months (95% CI: 12.9 to 17.8).¹²

Avelumab is the only immunotherapy licensed in the UK as monotherapy for the first-line maintenance treatment of locally advanced or metastatic UC in adults who are progression-free following platinum-based chemotherapy following the results from a Phase III trial demonstrating a statistically significant prolonging of median overall survival. This improvement in median OS represents a 31% reduction in the risk of death in the overall population (Hazard Ratio (HR) 0.69; 95% CI: 0.556 to 0.863; 2-sided p-value=0.001).¹²

JAVELIN Bladder 100 study found evidence to support both avelumab efficacy and safety and demonstrated an improvement in the median overall survival for eligible patients with locally advanced or metastatic bladder cancer in maintenance avelumab plus BSC compared to BSC alone.^11,12

Dr Olivia Ashman, Oncology Medical Director, Pfizer UK explains: “We are dedicated to developing innovative new treatments that can change patients’ lives. This advance in treatment offers patients affected by this devastating disease, the possibility of additional time with their families and friends.”

Following release of the SMC public notification, avelumab will become funded and available through NHS Scotland to eligible adult patients living in Scotland as monotherapy for first-line maintenance treatment of locally advanced or metastatic UC who are progression-free following platinum-based chemotherapy.

References

^[1] Chalasani V, et al. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can Urol Assoc J. 2009; 8; 193-8.

² Koufopoulou, M., Miranda, P., Kazmierska, P., Deshpande, S., & Gaitonde, P. (2020). Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options. Cancer Treatment Reviews, 89, 102072. doi: 10.1016/j.ctrv.2020.102072

³ Public Health Scotland Cancer Incidence in Scotland (to December 2018). Available at: https://publichealthscotland.scot/media/3597/2020-04-28-cancer-incidence-report.pdf (Last accessed July 2021)

⁴ Public Health Scotland (ISD Scotland). Cancer Statistics. Bladders Cancer. Available at: https://www.isdscotland.org/Health-Topics/Cancer/Cancer-Statistics/Bladder/#cancer-of-the-bladder (Last accessed July 2021)

⁵ De Santis M, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30:191–199.

⁶ Dogliotti L, et al. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007;52:134–141.

⁷ 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. J Clin Oncol 2005;23:4602-4608.

⁸ Von der Maase H, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Onc 2000;18:3068-77.

⁹ Chamie, MD, MSHS et. al. RECURRENCE OF HIGH-RISK BLADDER CANCER: A

POPULATION-BASED ANALYSIS. Cancer. 2013 September 1; 119(17): 3219–3227. doi:10.1002/cncr.28147

¹⁰ Cancer.net. Available at : https://www.cancer.net/navigating-cancer-care/how-cancer-treated/understanding-maintenance-therapy (Last accessed July 2021)

¹¹ Powles T, et. Al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18. PMID: 32945632.

¹² BAVENCIO® (avelumab) UK SmPC Electronic Medicines Compendium. (EMC). Bavencio 20 mg/mL concentrate for solution for infusion. Available at: https://www.medicines.org.uk/emc/product/8453/smpc. (Last accessed July 2021)

¹³ Alsaab H et al. PD-1 and PD-L1 checkpoint signalling inhibition for cancer immunotherapy: mechanism, combinations and clinical outcome. Front. Pharmacol. 2017;8:561

Job code: GB-AVEBL-00140

Date of preparation: July 2021