NICE Issues Evidence Based Recommendations on Nivolumab for Previously Treated Advanced RCC

Nivolumab as monotherapy is indicated for the treatment of advanced RCC after prior therapy in adults

On 23 November 2016, the NICE published a Technology appraisal guidance [TA417] on nivolumab for previously treated advanced renal cell carcinoma (RCC).Nivolumab is recommended, within its marketing authorisation, as an option for previously treated advanced RCC in adults, when the company provides nivolumab with the discount agreed in the patient access scheme.

Nivolumab extended overall survival compared with everolimus, but there was uncertainty about the extent of the survival benefit when measured over the long term.

Most of the incremental cost-effectiveness ratios (ICERs) for nivolumab compared with any comparator were below 50,000 GBP per quality-adjusted life year (QALY) gained. The appraisal committee acknowledged that scenarios assuming a greater long-term survival benefit reduced the ICERs. It concluded that, when applying the maximum weighting to the QALY that is possible under the end-of-life criteria, the ICER for nivolumab fell within the range of a cost-effective treatment.

What is the position of the treatment in the pathway of care for the condition?

For people who have had 1 previous treatment, nivolumab is a potential alternative to:

  • axitinib (which is offered to most people)
  • everolimus (which is offered to people who cannot have axitinib)
  • best supportive care (which is offered to people who cannot have axitinib or everolimus).

For people who have had 2 previous treatments, nivolumab is a potential alternative to best supportive care.

Availability, nature and quality of evidence

The evidence mostly came from CheckMate 025, an open-label randomised trial with 821 patients that compared nivolumab with everolimus. The company provided unpublished data from a phase I and a phase II trial (CheckMate 003 and CheckMate 010 respectively); these trials included longer-term follow‑up data on mortality.

Relevance to general clinical practice in the NHS

The committee concluded that the overall trial population of CheckMate 025 was similar to NHS patients and so the results were generalisable to the NHS.

Uncertainties generated by the evidence

The CheckMate 025 data were immature. The clinical experts advised that it was plausible that in the future an overall survival curve with a 'long tail' (that is, an extended survival benefit) would be shown for RCC treated with nivolumab, based on the results of nivolumab for melanoma. The committee considered the additional evidence from CheckMate 003 and CheckMate 010 presented by the company during consultation which showed longer-term survival for RCC with nivolumab but was concerned that the sample sizes were small. It concluded that the most robust results came from CheckMate 025, which showed that nivolumab extended life by a median of 5.4 months compared with everolimus, but that there was uncertainty about the extent of the survival benefit when measured over the long term.

Are there any clinically relevant subgroups for which there is evidence of differential effectiveness?

CheckMate 025 included a mix of people who had had 1 previous treatment with a tyrosine kinase inhibitor and people who had had 2 previous tyrosine kinase inhibitors. During consultation the company clarified that the treatment effect of nivolumab was clinically and statistically significant for both subgroups. The committee concluded that nivolumab prolonged overall survival compared with everolimus both for people who had had 1 previous treatment and people who had had 2 previous treatments.

Estimate of the size of the clinical effectiveness including strength of supporting evidence

CheckMate 025 showed that nivolumab extended life by a median of 5.4 months compared with everolimus, but there was uncertainty about the extent of the survival benefit when measured over the long term.

Data from CheckMate 003 and CheckMate 010 provided during consultation and clinical experts' opinion supported the expectation of a longer-term survival benefit, although it was uncertain how many patients, on average, this would affect.

Nivolumab (Opdivo, Bristol–Myers Squibb) is a human monoclonal antibody that blocks an immune checkpoint protein receptor, programmed cell death protein 1 (PD‑1) to promote an anti-tumour response.

Before the marketing authorisation was granted (April 2016), nivolumab was available in the NHS through the early access to medicines scheme.

The most common adverse reactions with nivolumab in clinical trials were tiredness, rash, pruritus, diarrhoea, nausea and decreased appetite (occurring in more than 10% of people).

Recommended dose and schedule is 3 mg/kg given intravenously every 2 weeks.

The list price is 439 GBP per 40‑mg vial or 1,097 GBP per 100‑mg vial.

The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of nivolumab, with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.