On 27 July 2016, NICE UK issued a technology appraisal guidance which recommends nivolumab in combination with ipilimumab within its marketing authorisation, as an option for treating advanced (unresectable or metastatic) melanoma in adults, only when the company provides ipilimumab with the discount agreed in the patient access scheme.
Nivolumab is a human monoclonal antibody (immunoglobulin G4) that blocks the programmed cell death‑1 receptor (PD‑1) and activates the immune system to attack cancer cells. Nivolumab is administered intravenously.
Ipilimumab is a fully human antibody that binds to cytotoxic T lymphocyte‑associated antigen 4 (CTLA‑4), a molecule expressed on T cells that plays a critical role in regulating natural immune responses. Ipilimumab is designed to block the activity of CTLA‑4 resulting in augmentation and prolongation of the T‑cell immune response.
Nivolumab in combination with ipilimumab has a UK marketing authorisation “for the treatment of advanced (unresectable or metastatic) melanoma in adults”. The final summary of product characteristics recommends that “treatment should be continued as long as clinical benefit is observed or until treatment is no longer tolerated”.
Evidence-based recommendations on nivolumab with ipilimumab for treating advanced melanoma in adults
The recommended starting dose of the combined regimen is nivolumab 1 mg per kilogram of body weight and ipilimumab 3 mg per kilogram of body weight, administered intravenously over a 90‑minute period every 3 weeks for a total of 4 doses. This is followed by maintenance treatment with nivolumab alone at a dose of 3 mg per kilogram body weight, administered intravenously over a 60‑minute period every 2 weeks.
The summary of product characteristics states that “relative to nivolumab monotherapy, an increase in progression‑free survival (PFS) for the combination of nivolumab with ipilimumab is established only in patients with low tumour PD‑L1 expression”.
It recommends that “before initiating treatment with the combination, physicians are advised to carefully evaluate the individual patient and tumour characteristics, taking into consideration the observed benefits and the toxicity of the combination relative to nivolumab monotherapy”. It also states that, “no clear cut‑off for PD‑L1 expression can reliably be established when considering the relevant endpoints of tumour response and PFS” and recommends that “treatment should be continued as long as clinical benefit is observed or until treatment is no longer tolerated”.
The most common adverse events in patients treated with nivolumab in combination with ipilimumab in the trials were fatigue, diarrhoea, itching, fever, colitis, nausea, increased transaminases and enlargement of the pituitary gland.
Nivolumab is available at a list price of £439 per 4‑ml (40‑mg) vial (excluding VAT). Ipilimumab is available at a list price of £3,750 per 10‑ml (50‑mg) vial and £15,000 per 40‑ml (200‑mg) vial (excluding VAT; British national formulary). The company has agreed a patient access scheme for ipilimumab with the Department of Health. This scheme provides a simple discount to the list price of ipilimumab 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.
You can read the full guidance here.
Next review date is foreseen in July 2018.