The UK Divide: Does having a Pembrolizumab-Chemotherapy option in head and neck cancer matter? Real-world experience of first-line palliative pembrolizumab monotherapy and pembrolizumab-chemotherapy combination in Scotland

Objectives The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma (HNSCC) in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence who approved monotherapy alone in England and Wales. We aimed to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma (HNSCC) in the palliative setting in Scotland. Materials and Methods We analysed the electronic records of patients who initiated pembrolizumab-containing treatment between 01/03/2020–30/09/2021. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DOR), disease control rate (DCR). Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival. Results Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to the KEYNOTE-048 study though our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease. For patients receiving monotherapy (n=76), 12-month and 24-month OS was 45% and 27%, respectively. For patients receiving pembrolizumab-chemotherapy (n=15), 12-month OS was 60% (24-month OS had not yet been reached). Experiencing ≥1 irAE (versus no irAEs), of any grade, was associated with favourable OS and PFS for patients receiving monotherapy in both univariable log-rank analysis (median OS 17.4 months versus 8.6 months, respectively, P=0.0033; median PFS 10.9 months versus 3.0 months, respectively, P<0.0001) and multivariable analysis (Cox proportional hazards regression: OS HR: 0.31, P=0.0009; PFS HR: 0.17, P<0.0001). Conclusion Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing irAEs are generally a positive marker of PD-L1 inhibitor response. ### Competing Interest Statement Christina Wilson reports an honoraria from MSD outwith this study. Rafael Moleron reports advisory boards for MSD and Vasodynamics. All remaining authors report no conflicts of interest. ### Funding Statement Claire Paterson is supported by NHS Research Scotland (NRS) senior fellowship, Beatson Cancer Charity and CRUK RadNet Glasgow. David Noble is supported by an NHS Research Scotland (NRS) senior fellowship, and the Jamie King Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The local National Health Service Information Governance team at the Beatson West of Scotland Cancer Centre waived ethical approval for this work on the grounds that the study collected anonymised health service clinical practice data only. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. * HNSCC : head and neck squamous cell carcinoma irAE : immune-related adverse event PD-L1 : programmed death-ligand 1