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Pembrolizumab for untreated metastatic or unresectable recurrent squamous cell head and neck cancer

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1 Recommendations

1.1 The committee is minded not to recommend pembrolizumab as an option for untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD‑L1 with a combined positive score (CPS) of 1 or more.

1.2 The committee recommends that NICE requests further clarification and analyses from the company, which should be made available for the next appraisal meeting. These should include the following for pembrolizumab monotherapy and pembrolizumab with platinum chemotherapy and 5‑fluorouracil (5‑FU):

  • Provide a full comparison of baseline patient characteristics for the 2 subgroups: people whose cancer started inside or outside the oral cavity. Highlight any imbalances in the baseline patient characteristics in each of the subgroups (see section 3.6).

  • Provide overall survival data (Kaplan–Meier curves, hazard ratios) for the 2 subgroups. Carry out formal statistical analysis to adjust for imbalances in baseline patient characteristics in the subgroups (see section 3.6). Justify which adjustment method was used and do not restrict it to just the covariates that are unbalanced (see NICE DSU technical support document 17).

  • Provide overall survival extrapolation curves, after adjusting for imbalances in baseline patient characteristics for the 2 subgroups (see section 3.10), and justify the choice of distribution curve used.

  • Provide an alternative utility value for progressed disease. This should come from published literature (see section 3.11).

  • Explore techniques to provide full incremental analyses for the 2 subgroups. The incremental analysis should incorporate all of the above, a 2-year stopping rule (see section 3.8), and a 5-year duration of treatment effect (see section 3.9). In addition, carry out alternative analyses using the company's fractional polynomial network meta-analysis and the evidence review group's approach of using data from KEYNOTE 048 for the comparison of pembrolizumab with platinum chemotherapy and 5‑FU (see section 3.7).

Why the committee made these recommendations

Treatment of metastatic or unresectable recurrent HNSCC depends on where it started. If it starts inside the oral cavity (mouth), it's usually first treated with cetuximab, platinum chemotherapy and 5-FU. If it starts outside the oral cavity it's treated with platinum chemotherapy and 5-FU.

Clinical trial evidence shows that people who have a type of metastatic or unresectable recurrent HNSCC defined as PD-L1 positive with a CPS of 1 or more live longer if they have pembrolizumab (on its own or with other chemotherapy drugs) than if they have cetuximab with platinum chemotherapy and 5-FU. But there's uncertainty over the evidence because the comparator drugs in the trial do not reflect what happens in the NHS in England. In the comparator arm of the trial all people were given cetuximab with platinum chemotherapy and 5-FU, regardless of whether the cancer started inside or outside the oral cavity. This is not established clinical practice in the NHS in England. Separate clinical evidence for people whose cancer started outside the oral cavity was not provided. Also, information about the clinical and cost effectiveness for the 2 different patient groups (cancer starting inside or outside the oral cavity) was incomplete. Therefore, NICE is unable to make a recommendation about pembrolizumab and has asked for more clinical and cost-effectiveness evidence.