Following the announcement that Merck & Pfizer’s immunotherapy drug avelumab has been approved by National Institute for Health and Care Excellence (NICE) in the UK, Lu Rahman speaks to Dr Stuart Hill, Medical Director for Merck, about the development of the drug and what this means for the treatment of bladder cancer.
The UK’s National Institute for Health and Care Excellence (NICE) recently overturned a previous decision not to recommend the immunotherapy BAVENCIO (avelumab) for the treatment of bladder cancer. The decision came after avelumab’s developers, Merck KGaA and Pfizer, appealed. The drug is now recommended as a maintenance treatment option in eligible adult patients with locally advanced or metastatic urothelial carcinoma (UC). The decision means that 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. “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,” says DrStuart Hill,Medical Director of,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.” Dr Olivia Ashman, Oncology Medical Director of, Pfizer UK, agrees: “We’re delighted to now have both the NICE and Scottish Medicines Consortium (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.”
The development of BAVENCIO has been a ground-breaking project to work on, according to Hill. “BAVENCIO (avelumab) is a human anti-programmed death ligand-1(PD-L1) antibody, which has been shown in preclinical models to engage both the adaptive and innate immune functions1. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated anti-tumour immune response in preclinical models2,” he adds.
Benefits of collaboration
Merck and Pfizer signed an agreement to co-develop and co-promote Bavencio in 2014. “The development programme focused on difficult to treat cancers, where there was high unmet clinical need, that were thought likely to respond to immunotherapy, based on early phase clinical data,” says Hill.
Several Phase III studies were then initiated, targeting genito-urinary cancers such as bladder and kidney cancers, non-small cell lung cancer, gastric cancer, and ovarian cancer3,4,5. “The resulting programme has led to approval for avelumab for use as monotherapy in adults with metastatic Merkel cell carcinoma (MCC), as first line maintenance therapy in adults with locally advanced or metastatic urothelial cellcarcinoma, who are progression-free after treatment with platinum-based chemotherapy, and in combination with axitinibin adults with advanced renal cell carcinoma (aRCC)6, so we are really proud of what has been achieved and the hard work of all the teams involved,” Hill explains.The collaboration between Merck and Pfizer has been key to the success of this drug. Hill reveals: “Without the co-development agreement, avelumab would never have come to market so quickly – it was essential to speed up the resourcing and development expertise. The global strategic alliance between Merck and Pfizer has been going since 2014 and it enabled the companies to greatly benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1antibody initially discovered and developed by Merck.” He adds that the alliance will continue to jointly develop and commercialise avelumab across different oncology specific therapeutic areas, developing high-priority international clinical programmes to further investigate the potential avelumab has, either as a monotherapy or as part of combination regimens, as we strive to find new ways to treat cancer.
NICE approval significance
The NICE approval is significant for bladder cancer survival rates. “Bladder cancer is the 11th most common cancer in the UK and the 10th most common cause of cancer death7,” says Hill. “Urothelial carcinoma (UC), accounts for more than 90% of bladder cancer cases 8and has poor survival outcomes9. The one-year survival rate for bladder cancer is the lowest for those patients diagnosed with advanced bladder cancer (stage4), with only 36% of patients at stage 4 surviving for at least one year10.” After publication of the Final Appraisal Document (FAD) by NICE on 7 April 2022 and in addition to the SMC’s approval in August 2021, this means that patients throughout the UK will now have access to treatment. Hill adds: “Unfortunately bladder cancer has high recurrence rates, up to 74.3%10 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 on. The latest data from JAVELIN Bladder 100 show an increase in median overall survival of 8.8 months over BSC, which represents a 24% reduction in the risk of death compared to BSC alone11,16.”
The significance of avelumab is that it is the only immunotherapy in the first-line maintenance setting to potentially help patients with locally advanced or metastatic urothelial carcinoma who are progression-free following platinum-based chemotherapy to live longer compared to BSC alone 11,15. “The majority of patients are currently treated with platinum-based therapy which does have high response rates, but these responses are not durable, leading to progression and relatively short survival12,13,14. By using avelumab after platinum-based chemotherapy in the maintenance phase before progression, the response is maintained for longer, which results in patients surviving for longer15,” says Hill. He adds that approximately 730 patients in England with locally advanced or metastatic urothelial carcinoma would be eligible for treatment with avelumab as monotherapy for first-line maintenance treatment who are progression free following platinum-containing chemotherapy.
Immunotherapy challenges
Looking at the wider immunotherapy market Hill sees several challenges ahead. “We see that in some cancers, biomarker testing may be needed to determine whether a patient is more likely to respond to an immunotherapy, but the type of test and the cut-off levels that determine use differ from one tumour to another. In the UK, biomarker testing for immunotherapies brings additional challenges: availability of tissue, training of qualified staff to do the testing, speed of testing, consistency of access and how testing is funded and positioned in the treatment pathway all pose distinct challenges. All of these components can impact how patients get the right treatment for their type of cancer and more importantly, how quickly they are able to get the treatment. These challenges are consistent across the board for immunotherapies, as well as the newer targeted therapies.”
Immunotherapies also provide different clinical challenges compared to conventional chemotherapies, so Hill recognises that more education and information for HCPs and patients is needed so that they understand the differences and are fully aware of the implications. For example, managing the side-effects of immunotherapies is a clinical challenge that can only be addressed if a wide group of HCPs are aware and understand how to appropriately manage them. “The toxicities associated with immunotherapies are very different from what healthcare professionals (HCPs) would experience with chemotherapy and can be critical to identify and treat appropriately, before they become serious. Education for both the patient and treating clinicians is therefore incredibly important,” he adds.
There is still a lot to learn on the long-term use of immunotherapies and Hill outlines the importance of continuing to evaluate the evidence to make sure we understand the drivers of treatment efficacy – ultimately enabling us to personalise treatment.
“Cancer growth is multifaceted and while immunotherapy is clearly a new way that we can prevent tumour growth and development, the combining and sequencing of treatments is going to be key to achieving optimal outcomes. If we can identify which patients will respond best to which treatment, and identify the right oncogenic drivers that are causing the cancer to grow and develop, we can target the right intervention to stop it. Immunotherapies have a huge role to play in the future of personalising treatments this way,” he states.
Hill says that the significant advances in cancer treatment in UC are reflected by changes to major bladder cancer treatment guidelines, such as the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO), who have started adopting the strategy of 1L maintenance avelumab after non-progression with platinum-based chemotherapy as the new Standard of Care 16,17.
The treatment landscape in bladder cancer continues to evolve. Enfortumab vedotin, an antibody-drug conjugate, directed against Nectin-4, looks promising, with good data in patients who have been previously treated with platinum-based therapy and an immune-checkpoint inhibitor18. There are already studies underway to see this treatment move to earlier in the treatment pathway, but how this treatment will be best used remains to be proven,” he says.
Volume 23 – Issue 3, Summer 2022
About the author:
Dr Stuart Hill is the Medical Director for Merck. In 1999, after completing a PhD in Chemistry, Hill joined the industry in a sales role with Servier, before progressing to marketing and management roles. In 2010, Hill joined Merck and has worked for the last 10 years in the Oncology Business, which he has led as Business Unit Director for the last 3.5 years. The heavy focus on translating science into improved outcomes for patients has inspired Hill to now take up the leadership of the Medical Affair steam for Merck’s UK & Ireland operation.
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