Scotland sees advance in treatment of kidney cancer with decision to fund first immunotherapy combination
• Decision based on data from Phase III head-to-head study stopped early due to an overall survival efficacy benefit versus sunitinib, a current standard of care
• The study demonstrated a 37% decreased risk of death in intermediate- and poor-prognostic risk patients compared to sunitinib
(Uxbridge, Middlesex, 10 June 2019) – Bristol-Myers Squibb Pharmaceuticals Limited today announced that the Scottish Medicines Consortium (SMC) has decided to fund the combination of Opdivo® (nivolumab) plus Yervoy® (ipilimumab) for use within NHS Scotland as a first-line treatment option for an advanced form of the most common type of kidney cancer,1,[vi] renal cell carcinoma (RCC), specifically in previously-untreated patients who are considered of intermediate- and poor-prognostic risk. This recommendation signifies an important landmark in the treatment landscape, representing the first approval of an Immuno-Oncology (I-O) combination therapy for first-line patients with this type of cancer in Scotland. I-O works by stimulating the body’s immune system to recognise and eliminate cancer cells.[vii]
In addition to the SMC decision announced today, the combination of nivolumab plus ipilimumab has recently been made available immediately for NHS patients in England via the Cancer Drugs Fund, and has also been approved for use in Wales and Northern Ireland.[viii]
RCC is currently the seventh most common cancer and rates have risen by approximately 47% over the last decade or so in the UK,[ix] which is faster than some other common cancers, including lung and bowel cancer.[x] In 2015, more than 12,500 people were diagnosed with kidney cancer in the UK9 and around 4,500 people die from the disease each year – an average of 12 people every day.[xi] In 2015, Scotland had the highest incidence rate of kidney cancer per head of population in the UK with more than 1,100 people diagnosed annually,[xii] 25-30% of whom have metastatic disease.6
“Having the combination of nivolumab and ipilimumab available is a step change in the treatment of advanced kidney cancer. It is great news to be able to treat our patients first-line with this immunotherapy combination, as it has been shown to help certain patients live longer and improve outcomes compared to a current standard of care”, said Dr Balaji Venugopal, Honorary Clinical Senior Lecturer, University of Glasgow.
The SMC recommendation is based on data from the Phase III CheckMate 214 study of 1,096 patients, which was stopped early after a planned interim analysis showed that the combination of nivolumab and ipilimumab demonstrated superior overall survival compared to sunitinib, a current standard of care.4,8 The co-primary outcome measures were overall survival, objective response rate and progression free survival in IMDC intermediate- and poor- prognostic risk patients:
• The combination of nivolumab (3mg/kg) plus low-dose ipilimumab (1mg/kg) demonstrated a significant improvement in overall survival, with a 37% decreased risk of death in intermediate- and poor-prognostic risk patients (n=425), compared to a current standard of care, sunitinib (n=422) (HR 0.63; 99.8% CI: 0.44 to 0.89; p<0.001). The overall survival benefit was observed regardless of PD-L1 expression level. The median overall survival was not yet reached at the point of analysis (95% CI: 28.2 to not estimable [NE]), compared to 26.0 months for patients treated with sunitinib (HR 0.63; 95% CI: 22.1 to NE; p<0.001)4
• The objective response rate was 42% (95% CI: 37 to 47) in the nivolumab plus ipilimumab arm, versus 27% (95% CI: 22 to 31) in the sunitinib arm (p<0.001). The complete response rate was 9% (n=40) in the nivolumab plus ipilimumab arm, versus 1% (n=5) in the sunitinib arm4
• The median progression-free survival was 11.6 months (95% CI: 8.7 to 15.5) and 8.4 months (95% CI: 7.0 to 10.8) respectively (HR 0.82; 99.1% CI: 0.64 to 1.05; p=0.03; not significant per the prespecified 0.009 threshold)4
• The combination therapy was associated with numerically fewer overall Grade 3 or 4 treatment-related adverse events compared to sunitinib (46% [n=250] versus 63% [n=335] respectively). The most common adverse events (>20%) in the combination arm included fatigue, pruritus, diarrhoea, rash and nausea. The most common immune-related adverse events requiring steroid treatment were pneumonitis (59%), hepatitis (35%) and nephritis and renal dysfunction (27%)4
“We are delighted that the SMC has accepted the combination of nivolumab plus ipilimumab as an important treatment option for Scottish advanced RCC patients who have an intermediate- and poor-prognostic risk. We will work closely with the SMC and NHS Scotland to support the swift implementation of this advice,” said Lynelle Hoch, General Manager, Bristol-Myers Squibb UK & Ireland. “By taking a collaborative approach to working with NICE and SMC we have been able to ensure this immunotherapy combination with the potential to extend life is available to all eligible patients, no matter where they are living in the UK.”
 As defined by criteria from the International Metastatic Renal Cell Carcinoma Database (IMDC) grading system.
[i] Cancer Research UK. Kidney Cancer. Types and Grades. Available at: https://www.cancerresearchuk.org/about-cancer/kidney-cancer/stages-types-grades/types-grades. Last accessed May 2019.
[ii] ISD Scotland. Cancer Incidence and Prevalence in Scotland (to December 2017). Available at https://www.isdscotland.org/Health-Topics/Cancer/Publications/2019-04-30/i_cancer_kidney.xls. Last accessed May 2019.
[iii] Motzer, R.J et al. 2013. Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma. N Engl J Med 2013; 369:722-731.
[v] Wagstaff, J et al. 2016. Treatment patterns and clinical outcomes in patients with renal cell carcinoma in the UK: insights from the RECCORD registry. Ann Oncol 2016; 27:159–165.
[vi] Scottish Medicines Consortium. nivolumab (Opdivo) SMC2153. Available at: https://www.scottishmedicines.org.uk/medicines-advice/nivolumab-opdivo-fullsubmission-smc2153/. Last accessed June 2019.
[vii] Cancer Research UK. What is immunotherapy? Available at: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/what-is-immunotherapy. Last accessed June 2019.
[viii] National Institute for Health and Care Excellence. Final appraisal document. Nivolumab with ipilimumab for untreated metastatic renal cell carcinoma [TA581]. Available at: https://www.nice.org.uk/guidance/ta581/documents/final-appraisal-determination-document. Last accessed June 2019.
[ix] Cancer Research UK. Kidney cancer incidence statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer/incidence#heading-Three. Last accessed June 2019.
[x] Cancer Research UK. Incidence trends over time for common cancers. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/common-cancers-compared#heading-Three. Last accessed June 2019.
[xi] Cancer Research UK. Kidney cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer#heading-One. Last accessed June 2019.
[xii] Kidney Cancer UK. Incidence of kidney cancer in the UK. Available at: https://www.kcuk.org.uk/kidneycancer/what-is-kidney-cancer/incidence-of-kidney-cancer-in-the-uk/. Last accessed June 2019.
- Mike Wood