NICE Recommends BAVENCIO® (Avelumab) in Combination with Axitinib for First-Line Treatment of Adult Patients with Advanced Renal Cell Carcinoma

Merck and Pfizer announced today that the National Institute for Health and Care Excellence (NICE) has recommended the immunotherapy BAVENCIO^® (avelumab) in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) for use within the Cancer Drugs Fund.

 

Kidney cancer is the seventh most common cancer in the UK.¹ Renal cell carcinoma (RCC) is the most common type, accounting for more than 8 out of 10 kidney cancers in adults.² Outcomes for patients with advanced RCC remain unacceptably poor, with a five-year survival rate of approximately 12% at the latest stage.¹ Most of the first-line treatment options NICE recommends for advanced RCC are targeted antiangiogenic therapies (e.g. tyrosine kinase inhibitor (TKIs))³ which many patients have inherent resistance to.⁴ About half of patients with metastatic RCC do not receive a second-line therapy,^5,6 for reasons including poor performance status or adverse events from initial treatment.^5,6,7 Therefore, more first-line treatment options are needed for advanced RCC patients from all prognostic groups.

 

Avelumab is an immune checkpoint inhibitor targeting PD-L1⁸ and axitinib is an antiangiogenic VEGF-targeted TKI.⁹ The combination of these treatments has complementary mechanisms of action, providing enhanced benefits by targeting two key pathways that tumours use to grow: inhibiting angiogenesis and stimulating the immune system’s anti-tumour responses.⁴

 

The JAVELIN Renal 101 study demonstrated that avelumab in combination with axitinib met the primary endpoint of significantly longer progression-free survival (PFS) in patients with PD-L1-positive clear cell advanced RCC, compared to patients who received sunitinib.⁸  

 

In the overall population, irrespective of PD-L1 status and across all prognostic risk groups, the combination significantly lowered the risk of disease progression or death by 31% (HR: 0.69 [95% CI: 0.574–0.825; p<0.0001]).¹⁰

 

It demonstrated superiority in PFS compared to sunitinib alone, improving median PFS in the overall population by 5.3 months (13.3 months [95% CI: 11.1-15.3] vs 8 months [95% CI: 6.7-9.8], HR 0.69 (0.57;0.83; p <0.0001)).¹⁰ The combination therapy also nearly doubled the objective response rate (ORR) compared with sunitinib (ORR; 52.5% [95% CI: 47.7-57.2] vs. 27.3% [95% CI: 23.2-31.6]).¹⁰ The study is ongoing to determine overall survival benefit.

 

Professor Amit Bahl, a consultant medical oncologist specialised in renal cell carcinoma, said:

“This positive recommendation from NICE provides patients with advanced Renal Cancer an effective and well tolerated treatment option with proven benefits in progression free survival and objective response rates from a randomised Phase 3 trial. This could improve outcomes in this group of patients. The combination of an immunotherapy with a tyrosine kinase inhibitor provides patients a novel treatment option.”

 

The incidence of kidney cancer in the UK has risen by 87% since the early 1990s, and it now accounts for 4% of all new cancer cases in the UK.¹ It is more common than cervical cancer and liver cancer combined.^1,11,12

 

Approximately 13,056 new cases of kidney cancer are diagnosed in the UK every year.¹ More than 4 in 10 patients are first diagnosed with kidney cancer at a late stage,¹ and 30% of patients treated for localised RCC at an earlier stage go on to develop tumour recurrence.¹³

 

Nick Turkentine, CEO of Kidney Cancer UK said: “We are delighted with NICE’s decision to give NHS patients access to this new combination therapy, as there is a real need to improve outcomes and increase treatment options for people with advanced renal cell carcinoma.”

The combination demonstrated a safety and tolerability profile consistent with the known safety profiles of avelumab and axitinib as monotherapy, and the frequency of adverse events is similar to treatment with sunitinib.⁴ In the overall population, 71.6% of those receiving combination therapy and 71.5% of those receiving sunitinib experienced at least one treatment-emergent adverse event of grade three or above.¹⁰

 

Dr Mike England, Medical Director, Merck UK & Ireland said: “Through our alliance with Pfizer, we are proud to be bringing innovation to a therapy area where there is a clear unmet need for new treatment options. This is the first immunotherapy and targeted antiangiogenic therapy combination recommended by NICE as a first-line option for patients with advanced RCC in England and Wales, who will now be able to access the potential enhanced benefits of combining these two types of treatment. We are working closely with healthcare professionals to support and help inform their treatment decisions during these unprecedented times, while continuing to provide patients with the best possible care.”

 

Immune checkpoint inhibitors are a type of immunotherapy that have shown promising results against a variety of cancers.¹⁴ By binding to PD-L1 on tumour cells, avelumab allows the immune system to recognise and kill tumour cells.⁸ Axitinib targets vascular endothelial growth factor (VEGF) receptors, which play a role in angiogenesis, tumour growth and metastatic progression.⁹

 

Dr Olivia Ashman, Oncology Medical Director, Pfizer UK said: “We are delighted with the decision to make this treatment available to UK patients. The combination has the potential to improve the lives of patients living with RCC as well as help healthcare professionals optimise their patients’ treatment. NICE’s positive recommendation also addresses the significant need for first-line treatments with a benefit across all prognostic risk groups.”

 

Avelumab in combination with axitinib was made available as part of the Early Access to Medicines Scheme (EAMS) in August 2019. This has allowed more than 150 patients to gain earlier access to this innovative combination treatment throughout the UK.

 

As NICE has now published its Final Appraisal Document, the combination is immediately available to NHS patients in England and Wales via the Cancer Drugs Fund.

 

medicine is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events.  Reporting forms and information can be found at mhra.gov.uk/yellowcard. Adverse events should also be reported to Merck Serono Limited on 0208 818 7373 (email: medinfo.uk@merckgroup.com)

 

About the JAVELIN Renal 101 Study

Bavencio plus axitinib was approved for this indication by the European Commission based on interim data from the ongoing Phase III JAVELIN Renal 101 study; a randomised, multicentre, open-label study of avelumab in combination with axitinib in 886 patients with untreated advanced RCC with a clear cell component. The study included patients across risk groups (International Metastatic Renal Cell Carcinoma Database Consortium [IMDC]: 21% favourable, 62% intermediate and 16% poor). The primary efficacy endpoints were progression-free survival (PFS) as assessed by a Blinded Independent Central Review (BICR) using RECIST v1.1 and overall survival (OS) in the first-line treatment of patients with advanced RCC who have PD-L1-positive tumours (PD‑L1 expression level ³1%). If PFS was statistically significant in patients with PD-L1-positive tumours, it was then assessed in all patients irrespective of PD-L1 expression. PFS based on BICR assessment per RECIST v1.1 and OS irrespective of PD‑L1 expression, objective response, time to response (TTR), duration of response (DOR) and safety are included as secondary endpoints. The JAVELIN Renal 101 study is ongoing as patients continue to be followed for overall survival.

 

About EAMS

The Early Access to Medicines Scheme (EAMS) aims to provide earlier availability to promising new unlicensed medicines for UK patients with high unmet clinical need. A full assessment of the quality, safety and efficacy of the treatment is conducted by the Medicines and Healthcare products Regulatory Agency’s assessment teams.

 

About PD-L1

PD-L1 is a protein expressed on the surface of cells, which binds to PD-1 receptors on T cells of the immune system to stop them from attacking them. Some tumour cells also have PD-L1 proteins on their surface (‘PD-L1 positive’ status), preventing the immune T cells from recognising and attacking them.¹⁵ BAVENCIO is an antibody which binds to PD-L1 on tumour cells and blocks it from binding to the PD-1 receptors on T cells, allowing the immune system T cells to recognise and kill the cancer cells.⁸

 

About the Merck-Pfizer Alliance

The global strategic alliance between Merck and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance will jointly develop and commercialise avelumab. The alliance is focused on developing high-priority international clinical programmes to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

 

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 52,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – Merck is everywhere. In 2018, Merck generated sales of    €14.8 billion in 66 countries.

 

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials.

 

Pfizer: Breakthroughs that change patients’ lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. In the UK, Pfizer has its business headquarters in Surrey and is a major supplier of medicines to the NHS. To learn more about our commitments, please visit us at www.pfizer.co.uk or follow us on Twitter (@Pfizer_UK) and Facebook (@PfizerUK).

 

 

¹ Cancer Research UK. Kidney Cancer Statistics https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer/incidence [Accessed February 2020]

² Cancer Research UK. Types and grades.  https://www.cancerresearchuk.org/about-cancer/kidney-cancer/stages-types-grades/types-grades [Accessed March 2020]

³ NICE. First-line treatment for advanced and metastatic renal cancer. Renal cancer overview- NICE pathways: https://pathways.nice.org.uk/pathways/renal-cancer#content=view-node%3Anodes-first-line-treatment-for-advanced-and-metastatic-renal-cancer [Last accessed February 2020]

⁴ Motzer R et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. The New England Journal of Medicine 2019;380(12):1103-1115

⁵ Eggers H, Ivanyi P, Hornig M, Grünwald V. Predictive factors for second-line therapy in metastatic renal cell carcinoma: a retrospective analysis. J Kidney Cancer VHL. 2017;4(1):8-15

⁶ Eichelberg C et al. SWITCH: A randomised, sequential, open-label study to evaluate the efficacy and safety of sorafenib-sunitinib versus sunitinib-sorafenib in the treatment of metastatic renal cell cancer. Eur Urol. 2015;68;837-847

⁷ Motzer RJ et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32:2765-2772

⁸ BAVENCIO® (avelumab) UK SmPC: https://www.medicines.org.uk/emc/product/8453/smpc [Last accessed May 2020]

⁹ INLYTA (axitinib) UK SmPC https://www.medicines.org.uk/emc/product/4325/smpc [Last accessed May 2020]

¹⁰ European Medicines Agency. Bavencio European Public Assessment Report: https://www.ema.europa.eu/en/documents/variation-report/bavencio-h-c-004338-ii-0009-g-epar-assessment-report-variation_en.pdf [Last accessed May 2020] 

¹¹ Cancer Research UK. Cervical cancer statistics. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/cervical-cancer#heading-Zero [Last accessed May 2020]

¹² Cancer Research UK. Liver cancer statistics. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/liver-cancer#heading-Zero [Last accessed May 2020]

¹³ Klatte T, Rossi SH, Stewart GD. Prognostic factors and prognostic models for renal cell carcinoma: a literature review. World J Urol. 2018;36(12):1943-1952

¹⁴ Singh S et al. Immune checkpoint inhibitors: a promising anti-cancer therapy. Drug Discovery Today. 2020;25(1):223-229

¹⁵ 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