The National Institute for Health and Care Excellence (NICE) announced updated guidance on the use of nivolumab (Opdivo, Bristol Myers Squibb) in combination with platinum-based chemotherapy for previously untreated advanced oesophageal squamous cell carcinoma (OSCC).
Standard first line treatment for unresectable advanced, recurrent, or metastatic OSCC is fluoropyrimidine-based and platinum-based chemotherapy. Some patients are treated with pembrolizumab plus chemotherapy if their tumours express PD L1 with a combined positive score (CPS) of 10 or more.
Diagnosis Usually at Advanced Stage With Poor Prognosis
There are no screening tools to identify OSCC, which is often diagnosed at an advanced stage and has a poor prognosis – it is less survivable than other cancers. The condition and its treatment side effects "massively affect patients' quality of life, social experience and relationships with family and carers", NICE said. It agreed with clinical experts and patients that there was "an unmet need" for an alternative treatment in people for whom pembrolizumab plus chemotherapy was not suitable.
In addition, some clinicians had said they would value an additional treatment option "because there may be circumstances in which nivolumab is preferred over pembrolizumab". NICE noted that suitability for nivolumab and pembrolizumab was assessed by measuring PD-L1 status, but the way that PD-L1 positivity was measured and defined differed in the marketing authorisations for the two drugs. Both nivolumab and pembrolizumab were suitable for some people. The committee acknowledged the overlap, and the differences between the two tests, with the complexity that introduces. In clinical practice, treatment decisions for OSCC might vary between different hospitals, the company had said.
NICE said that tests for suitability of nivolumab – ie tumours that expressed PD-L1 at 1% or more – or pembrolizumab (PD-L1 expression with CPS of 10 or more) should be done at the same time "to minimise any unnecessary delays in accessing treatment".
In its final appraisal document it recommended nivolumab with fluoropyrimidine-based and platinum-based combination chemotherapy within its marketing authorisation as an option for untreated unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma in adults whose tumours express PD-L1 at a level of 1% or more.
Nivolumab is recommended only if:• pembrolizumab plus chemotherapy is not suitable• the company provides nivolumab according to the commercial arrangement.
Treatment Extends Life and Time to Progression
NICE said that clinical trial evidence showed that for people whose tumours express PD-L1 at a level of 1% or more, nivolumab plus chemotherapy increased how long they lived compared with chemotherapy alone, and also increased time to progression.
However cost-effectiveness estimates with pembrolizumab were uncertain, NICE said. "Nivolumab plus chemotherapy has only been indirectly compared with pembrolizumab plus chemotherapy. Uncertainty in this comparison means it is difficult to determine which combination is more effective. The cost-effectiveness estimates for nivolumab compared with pembrolizumab are also uncertain, but nivolumab is unlikely to be cost effective compared with pembrolizumab."
Therefore nivolumab was recommended for routine use only when pembrolizumab is unsuitable.
"When compared with chemotherapy alone, nivolumab plus chemotherapy meets NICE's criteria to be a life-extending treatment at the end of life. Taking this into account, the cost-effectiveness estimates are likely within what NICE considers an acceptable use of NHS resources for this group. Therefore, nivolumab plus chemotherapy is recommended when pembrolizumab plus chemotherapy is unsuitable."
In this situation, and despite the remaining areas of uncertainty, NICE agreed that the cost-effectiveness estimates for nivolumab were likely to be "within the range usually considered a cost-effective use of NHS resources" given that "this is for a life-extending treatment for people with short life expectancy".
A spokesperson for NICE noted that the company had estimated that after NICE's decision, just over 300 people could benefit from the treatment. "NICE is determined to get the best care to patients fast, while ensuring value for money for the taxpayer, and at the same time creating useful and useable advice for the NHS."
Nivolumab is given by infusion and has a list price of £1,097 for a 100-mg vial (excluding VAT), but the maker is supplying it to the NHS under a confidential commercial arrangement.
The appeal period for the current appraisal will close at 5pm on 19 January 2023 and final draft guidance is expected on 8 February 2023.