Merck and Pfizer announced today that the National Institute for Health and Care Excellence (NICE) has recommended the immunotherapy 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.

Renal cell carcinoma (RCC) is the most common type, accounting for more than 8 out of 10 kidney cancers in adults.

Outcomes for patients with advanced RCC remain unacceptably poor, with a five-year survival rate of approximately 12% at the latest stage.

Most of the first-line treatment options NICE recommends for advanced RCC are targeted antiangiogenic therapies (e.g. tyrosine kinase inhibitor (TKIs)) which many patients have inherent resistance to.

About half of patients with metastatic RCC do not receive a second-line therapy, for reasons including poor performance status or adverse events from initial treatment.

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.

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.

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.

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]).

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)).

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]).

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.

It is more common than cervical cancer and liver cancer combined.

Approximately 13,056 new cases of kidney cancer are diagnosed in the UK every year.

More than 4 in 10 patients are first diagnosed with kidney cancer at a late stage, and 30% of patients treated for localised RCC at an earlier stage go on to develop tumour recurrence.

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.

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.

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.

By binding to PD-L1 on tumour cells, avelumab allows the immune system to recognise and kill tumour cells.

Axitinib targets vascular endothelial growth factor (VEGF) receptors, which play a role in angiogenesis, tumour growth and metastatic progression.

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.

Source: Merck and Pfizer