SMC accepts BAVENCIO® (Avelumab) in Combination with Axitinib for the First-Line Treatment of Adult Patients with Advanced or Metastatic Renal Cell Carcinoma

Merck and Pfizer announced today that the Scottish Medicines Consortium (SMC) has accepted the immunotherapy BAVENCIO^® (avelumab) for use within NHS Scotland in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

Kidney cancer is the seventh most common cancer in Scotland,^1,2 with approximately 1,200 new cases diagnosed every year.³  Rates are expected to soar by more than 70 per cent in the next 20 years.⁴ Renal cell carcinoma (RCC) is the most common type, accounting for more than 8 out of 10 kidney cancers in adults.⁵ Outcomes for patients with advanced RCC remain unacceptably poor, with a five-year survival rate of approximately 12% at the latest stage.¹

Avelumab is an immune checkpoint inhibitor (a type of immunotherapy that has shown promising results against a variety of cancers⁶) targeting PD-L1⁷ and axitinib is an antiangiogenic vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitor (TKI).⁸ These treatments have 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.¹⁰ By binding to PD-L1 on tumour cells, avelumab allows the immune system to recognise and kill tumour cells,⁷ while axitinib targets VEGF receptors, which play a role in angiogenesis, tumour growth and metastatic progression.⁸

Most of the first-line treatment options for advanced RCC are targeted antiangiogenic therapies (e.g. TKIs)⁹ which many patients have inherent resistance to.¹⁰ About half of patients with metastatic RCC do not receive a second-line therapy,^11,12  for reasons including poor performance status or adverse events from initial treatment.^11,12,13 Therefore, more first-line treatment options are needed for advanced RCC patients.

Dr Bala Venugopal, Consultant Medical Oncologist at The Beatson West of Scotland Cancer Centre, Glasgow, said: “Advanced renal cancer is a lethal disease and there is a need for better treatment options. To have the combination of avelumab and axitinib accepted as a new treatment option across all prognostic risk groups in patients with advanced kidney cancer by the SMC is a positive step in improving patient outcomes and quality of life.”

Professor James Larkin, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and supporter and Trustee of the Kidney Cancer Support Network said:

“Today’s announcement is excellent news and this approval is an important advancement for patients with advanced kidney cancer, improving their access to this promising new treatment. This first line combination therapy will make a real difference to patients and their quality of life. Clinical trials, including the JAVELIN Renal 101 trial have shown that avelumab plus axitinib is superior to previous standards of care with significantly lowered risk of disease progression and an improved rate of progression free survival. This latest development is another great example of the work the health community and research is doing to improve access to cancer treatments.”

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.⁷  

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]).¹⁴

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)).¹⁴ 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]).¹⁴ The study is ongoing to determine overall survival benefit.

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.¹⁰ 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.¹⁴

Dr Mike England, Medical Director, Merck UK & Ireland said: “We are delighted that the SMC has accepted the combination as an important treatment option for advanced RCC patients in Scotland. We will work closely with the SMC and NHS Scotland to support swift implementation and ensure eligible patients access the potential enhanced benefits of combining these two types of treatment. We continue to work with healthcare professionals to support and help inform their treatment decisions during these unprecedented times.”

Dr MH Ruhe Chowdhury, PhD, Interim Oncology Medical Director, Pfizer UK said: “By taking a collaborative approach to working with NICE and SMC we have been able to ensure this immunotherapy combination is available to all eligible patients , continuing our commitment to providing patients with the best possible care.”

Avelumab in combination with axitinib was made available as part of the Early Access to Medicines Scheme (EAMS) in August 2019. This has allowed over 180 patients to gain earlier access to this innovative combination treatment throughout the UK. When the EAMS was due to close in November 2019, Merck and Pfizer worked with NHS Scotland to secure continued access for patients, until an SMC decision through the Free of Charge Scheme.

In July 2020, National Institute for Health and Care Excellence (NICE) recommended avelumab in combination with axitinib for the first-line treatment of adult patients with advanced RCC for use within the Cancer Drugs Fund.

Following release of the SMC public notification, avelumab will become funded and available immediately through the NHS to adult Scottish patients with advanced renal cell carcinoma.

References

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

2 Public Health Scotland. Data and intelligence https://beta.isdscotland.org/find-publications-and-data/conditions-and-diseases/cancer/cancer-incidence-in-scotland/28-april-2020/ [Last accessed September 2020]

3 Kidney Cancer UK. Incidents of Kidney Cancer in the UK. https://www.kcuk.org.uk/incidents-of-kidney-cancer-in-the-uk/ [Last accessed September 2020]

4 Kidney Cancer UK. News – Scotland. Scots cancer rates to ‘rise by third over 20 years’. 2015 https://www.kcuk.org.uk/scotland/news-scotland/ [Last accessed September 2020]

5 Cancer Research UK. Types and grades.  https://www.cancerresearchuk.org/about-cancer/kidney-cancer/stages-types-grades/types-grades [Last accessed September 2020]

⁶ Singh S et al. Immune checkpoint inhibitors: a promising anti-cancer therapy. Drug Discovery Today. 2020;25(1):223-229

⁷ BAVENCIO® (avelumab) UK SmPC: https://www.medicines.org.uk/emc/product/8453/smpc [Last accessed September 2020]

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

9 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 September2020]

10 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

11 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

12 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

13 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

14 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 September 2020] 

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