The National Institute for Health and Care Excellence said in draft guidance released Wednesday that it will not recommend Merck & Co.'s Keytruda (pembrolizumab) as an option to treat first-line metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC), either as monotherapy or in combination. EU regulators approved Keytruda for this indication last November, making it the first anti-PD-1 treatment option in Europe for this patient population.
The approval was based on findings from the Phase III KEYNOTE-048 trial, which had met its primary endpoint of overall survival (OS). Results presented at last year's ASCO annual meeting showed that Keytruda plus chemotherapy cut the risk of death by 35% versus the EXTREME regimen, consisting of Merck KGaA's Erbitux (cetuximab) plus 5-fluorouracil and platinum-based chemotherapy, in certain HNSCC patients whose tumours expressed PD-L1 with a combined positive score (CPS) of one or more.
In its appraisal document, NICE is seeking further clarification and analyses from Merck regarding Keytruda monotherapy or its use with platinum chemotherapy and 5-fluorouracil, including OS data for two subgroups of patients depending on whether their cancer started inside or outside the oral cavity.
According to The Institute of Cancer Research (ICR), which criticised NICE's decision, UK clinical practice differs from the rest of the world in that oral cavity cancers are treated with the EXTREME regimen, while other head and neck cancers are treated with just the two chemotherapies. As a result, NICE said the KEYNOTE-048 trial, which grouped all forms of head and neck cancer together irrespective of their location and used the EXTREME regimen as the comparison arm, "was not wholly applicable to NHS practice." The agency added that "because current treatment options are different for cancer that started inside or outside the oral cavity, the [NICE appraisal] committee concluded that it would like to see all clinical and cost-effectiveness analyses by primary tumour location."
Kevin Harrington, professor of biological cancer therapies at the ICR, said NICE's decision "brings the UK further out of step with clinical practice in the rest of the world, where cancers of the mouth are treated in the same way as other head and neck cancers." He argued there is "clear evidence" that Keytruda has survival benefits for patients with HNSCC, and urged the agency to "revisit the evidence for the benefits of Keytruda, and to work with the drug company on a suitable compromise."
Keytruda carries a price of £2630 ($3426) for a 100mg vial in the UK, although NICE noted that it has a commercial agreement with Merck under which the company makes the product available to the NHS at an undisclosed discount. NICE indicated that the closing date for comments on the draft guidance is February 5.
The FDA approved Keytruda as monotherapy and as part of a combination last June for the first-line treatment of patients with HNSCC.
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