Association between immune-related adverse events and clinical outcomes for head and neck squamous cell carcinoma treated with first-line palliative pembrolizumab monotherapy or in combination with chemotherapy: a national, multi-centre, real-world, retrospective cohort study

Abstract 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.