• Following publication of the positive appraisal consultation document (ACD), lenvatinib plus pembrolizumab is now available to eligible people living in England
• There are approximately 13,300 new kidney cancer cases in the UK every year1
• In the UK, there has been an almost 88% increase in the incidence rate of kidney cancer since the early 1990s and approximately 9 in 10 of these cases are renal cell carcinomas1, 2
• Approximately one-third (36%) of people in the UK who are diagnosed with kidney cancer were diagnosed at an advanced or metastatic stage of the disease (stage 3 or 4)3 when the prognosis is significantly worse 4

The National Institute for Health and Care Excellence (NICE) has published an appraisal consultation document (ACD) recommending the use of lenvatinib, the oral multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus pembrolizumab, MSD’s anti-PD-1 therapy, as a therapeutic option for untreated intermediate or poor risk advanced renal cell carcinoma (RCC) in adults, only if nivolumab with ipilimumab would otherwise be offered. 5 This follows the Scottish Medicines Consortium’s positive recommendation of the combination for advanced RCC in June 2022.6 This combination will receive interim funding in England via the Cancer Drugs Fund until the publication of the technology appraisal guidance, which is expected in early 2023.

Lenvatinib is indicated for the treatment of adults with advanced renal cell carcinoma in combination with pembrolizumab, as first-line treatment.7 RCC is the most common type of kidney cancer, accounting for approximately 9 in 10 kidney cancer cases in the UK. 2 Between 2013 and 2017, approximately one-third (36%) of people in the UK were diagnosed with kidney cancer and followed up with until 2018, were diagnosed at an advanced or metastatic stage of the disease (stage 3 or 4). 3 It has the highest mortality rate of the genitourinary cancers, as more than a third of patients with RCC will die from the disease8, therefore, providing more treatment options for people with advanced RCC remains a priority.

“We are happy to have supported Eisai’s clinical trial programme, to help develop this alternative first-line combination therapy and are delighted to see NICE deliver a positive ACD, now making this treatment available to patients across England,” said Professor Thomas Powles, Director of Barts Cancer Centre at St. Bartholomew’s Hospital. “With more treatment options available to patients in more countries, we can provide personalised care plans that align more closely to their needs.”

“We are delighted that NICE is recommending this alternative first-line combination treatment option for patients living with advanced kidney cancer across England. We know through our annual Kidney Cancer UK patient survey that 42% of patients in the UK are diagnosed at an advanced stage when survival rates are typically lower. Having this combination option available through the Cancer Drugs Fund is great news which will be welcomed.” said Nick Turkentine, Chief Operating Officer, Kidney Cancer UK.

The decision by NICE is based on data from the Phase 3 trial: CLEAR (Study 307) / KEYNOTE581, which demonstrated statistically significant improvements versus sunitinib in progression-free survival and overall survival among adults with advanced RCC. 9 The trial’s primary endpoint was progression-free survival and secondary endpoints were overall survival and objective response as assessed by an independent review committee. 9 Progression-free survival (PFS) was longer with

lenvatinib plus pembrolizumab than with sunitinib, with a median PFS of 23.9 months versus 9.2 months for sunitinib (HR=0.39 [95% CI, 0.32-0.49]; p<0.001). Overall survival was also longer with lenvatinib plus pembrolizumab than with sunitinib, with 79.2% of patients in the lenvatinib and pembrolizumab group versus 70.4% of patients in the sunitinib group alive at 24 months s (HR=0.66 [95% CI, 0.49-0.88]; p=0.005). 9 The most common adverse events (all grades ?25%) for lenvatinib plus pembrolizumab were diarrhoea (61%), hypertension (55%), hypothyroidism (47%), decreased appetite (40%), fatigue (40%), nausea (36%), stomatitis (35%), dysphonia (30%), weight loss (30%), proteinuria (30%), PPE syndrome (29%), arthralgia (28%), rash (27%), vomiting (26%) and constipation (25%). 9

“We are delighted that NICE is issuing a positive ACD for lenvatinib in combination with pembrolizumab as an alternative first-line treatment option in kidney cancer,” said Pam Ganju, Vice President, Oncology Alliance Management & Business Unit Director, Eisai UK & Ireland. “The joint clinical development programme for these compounds has been specifically designed to address the unmet need in some of the most difficult-to-treat cancers, and the availability of this combination through NHS England is fantastic news for kidney cancer patients.”

David Long, Executive Director of Oncology, MSD UK said: “We are pleased to have worked with Eisai and the NHS to bring forward this alternative treatment option for kidney cancer patients. Despite kidney cancer being in the top ten most common cancers, there have been few new treatment options, and widespread variation in care, as seen in a report from Kidney Cancer UK last month. This makes today’s approval especially meaningful as we hope that this new treatment option will continue to raise the profile of kidney cancer and lead to better outcomes for patients.”