Merck and Pfizer have announced that, following a successful appeal of the prior Final Appraisal Document (FAD), the National Institute for Health and Care Excellence (NICE) has overturned its decision and now recommends the immunotherapy, avelumab, as a maintenance treatment option in eligible adult patients with locally advanced or metastatic urothelial carcinoma (UC), also known as bladder cancer.

The decision is welcomed as avelumab is the first and only monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic UC who are progression-free following platinum-based chemotherapy and now offers a further treatment option for these patients.

The NICE recommendation enables eligible patients in England, Wales and Northern Ireland to access this treatment via routine NHS funding. Interim funding via the Cancer Drugs Fund will enable reimbursement of avelumab until NICE final guidance is published and funded after a 30-day mandatory period.

Lydia Makaroff of Fight Bladder Cancer, explains: "We are delighted with this decision. Until now, there was no maintenance treatment available on the NHS in England, Wales and Northern Ireland for advanced bladder cancer after chemotherapy. This positive decision may have the potential to give hundreds of people with terminal bladder cancer more good quality time with their loved ones."

Bladder cancer is the 11th most common cancer in the UK and the 10th most common cause of cancer death. UC, which accounts for 90% of bladder cancer cases, has poor survival outcomes. 

The one-year survival rate for bladder cancer is the lowest for those patients diagnosed with advanced bladder cancer (stage 4), with only 36% of patients at stage 4 surviving for at least one year.

Dr Simon Crabb, Associate Professor in Medical Oncology, Cancer Sciences, University of Southampton Faculty of Medicine, states: “This is the only first-line maintenance monotherapy for advanced urothelial carcinoma following platinum-based chemotherapy and is a significant step forward in treating these patients with high unmet needs. NICE’s decision will provide healthcare professionals with an additional treatment option to help sustain and extend the benefits of platinum-based chemotherapy, potentially increasing overall survival and, importantly, without negatively affecting the patients’ quality of life.”

Bladder cancer has high recurrence rates (up to 74.3%), with most patients ultimately experiencing disease progression within nine months of initiation of first-line chemotherapy treatment.

The Phase III JAVELIN Bladder 100 study demonstrated that if patients, whose cancer does not progress after initial platinum-based chemotherapy, are given avelumab as maintenance treatment, together with best supportive care (BSC), it takes longer for their cancer to get worse, and they live longer than if they have BSC alone.

“We are very pleased that NICE’s revised decision to recommend avelumab as a maintenance treatment option for advanced bladder cancer means that eligible patients now have access to this much-needed treatment.” said Dr Stuart Hill, Medical Director, Merck UK & Ireland.

“The Merck-Pfizer Alliance is particularly grateful for the support of both the patient and clinical communities who came together during the process to highlight the need for physicians to be able to initiate patients on this innovative treatment approach.”

Results from the Phase III JAVELIN Bladder 100 study, that were submitted to NICE (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 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 17.9)).

The median duration of trial treatment was 24.9 weeks (range, 2.0 to 159.9) in the avelumab group and 13.1 weeks (range, 0.1 to 155.6) in the control group.

This statistically significant improvement in median OS represents a 31% reduction in the risk of death in favour of avelumab + BSC compared with BSC alone (Hazard Ratio (HR): 0.69; 95% CI: 0.56 to 0.86; 2-sided p-value=0.001).

Long-term follow-up data presented at the 2022 ASCO Genitourinary Cancers Symposium showed that median OS in the overall population was 23.8 months (95% CI: 19.9 to 28.8) in the avelumab + BSC arm vs 15.0 months (95% CI: 13.5 to 18.2) in the BSC alone arm (HR: 0.76 [0.631-0.915]; 2-sided p-value=0.0036), from a data cut-off date of 4 June 2021. The median duration of avelumab treatment was 25.3 weeks (range 2.0-216.0).

JAVELIN Bladder 100 study and the longer term follow up data 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.

The most common adverse events (AEs) of any grade and from any cause, that occurred in ≥10% patients in the avelumab group, include fatigue (n=61 [17.7%]) and pruritis (n=59 [17.2%]). 101 (29.4%) avelumab-treated patients had an adverse event that was categorised as being immune-related.

The most frequent category of immune-related adverse events was thyroid disorders (n=42 [12.2%]). High dose glucocorticoids were administered after an immune-related adverse event in 31 patients (9.0%) who received avelumab. Long-term follow-up data identified no new safety signals or concerns.

Dr Olivia Ashman, Oncology Medical Director, Pfizer UK explains: “We’re delighted to now have both the NICE and SMC recommendations for avelumab as a first-line maintenance therapy in advanced bladder cancer, enabling all eligible patients in the UK to have routine access to this innovative treatment on the NHS.  We’re committed to advancing science as well as ensuring access to the resulting treatments to improve the outlook for people living with cancer.” 

Source: National Institute for Health and Care Excellence (NICE)