Abstract
BackgroundImmunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma (cSCC). It is important to understand both safety and efficacy in a real-world and trial-ineligible cSCC population. We aimed to evaluate safety, efficacy and molecular insights among a broader cSCC population, including immunosuppressed patients, treated with immune checkpoint inhibitors (CPI).MethodsWe present a cohort of advanced cSCC patients (n = 61) treated from 2015 to 2020 evaluating the best overall response (BOR) (RECISTv1.1) to CPI therapy, immune-related adverse events (irAEs) and tumour mutational burden (TMB) to correlate with outcomes. A validated geriatric scoring index (CIRS-G) was utilised to assess comorbidities among patients ≥75. These data were compared with published clinical trial results among the broader cSCC population.ResultsBOR to CPI was lower among the entire cohort when compared with trial data (31.5 vs. 48%, P < 0.01), with higher rates of progression (59 vs. 16.5%, P < 0.01), regardless of immunosuppression history or age. Grade 3+ irAEs were more common among responders (P = 0.02), while pre-treatment lymphocyte count and TMB predicted response (P = 0.02).ConclusionsWe demonstrate comparatively lower response rates to CPI among real-world cSCC patients not explained by older age or immunosuppression history alone. Immune-related toxicity, absolute lymphocyte count and TMB predicted CPI response.
Highlights
Immunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma
While recent series have emerged that report comparable efficacy and favourable safety when using immunotherapy among challenging and trial-ineligible patients with other solid tumour types,[7,8,9] we present real-world data about efficacy, safety and molecular features among cutaneous squamous cell carcinoma (cSCC) patients treated with checkpoint inhibitor (CPI), focusing on elderly patients and those with a history of immunosuppression
We had hypothesised that the lower-than-predicted Overall survival (OS) we observed was impacted by competing comorbidities, and so we explored cumulative mean CIRS-G comorbidity and Eastern Cooperative Oncology Group (ECOG) performance scores
Summary
Immunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma (cSCC). While prior cSCC studies using CPIs included some patients 75 years and older, patients with immune compromise or immunosuppression needs (human immunodeficiency virus [HIV], haematologic malignancies and solid organ transplant [SOT] recipients) and active autoimmune conditions (requiring therapy within the last 5 years) were excluded. It remains unclear if the benefit and toxicity profile of these agents are generalisable to our oldest or most vulnerable patients in the face of incurable skin cancer
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