Background Immune checkpoint inhibitors (ICI) have resulted in high response rates in unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC). Large nerve perineural invasion (LN-PNI) in cSCC of the head and neck are associated with a poor prognosis and current response criteria for systemic therapy such as RECIST 1.1 are poorly suited to LN-PNI.
Objective To determine programmed death (PD)1 inhibitor response in cSCC patients with LN-PNI by correlating symptomatic response and radiological findings to clinically meaningful outcome measures.
Methods This multi-centre retrospective observational study enrolled 30 patients with biopsy or radiologically confirmed cSCC with LN-PNI treated with PD1 inhibitors between September 2017 and Nov 2022. Radiological disease progression (RDP) was defined as proximal extension of existing PNI or new sites of disease on Magnetic Resonance (MR) or Computerised Tomography (CT) imaging. Symptomatic response was defined as patient reported improvement in baseline symptoms including neuropathic pain.
Results
Of the 30 patients enrolled, 27 (90%) patients presented with symptoms at baseline; neuropathic pain in 25 (77.4%), facial weakness in 9 (30%), ophthalmoplegia in 4 (13%) and dysphagia in 1 (3%) patient. Prior treatment with surgery and/or radiation therapy for LN-PNI was administered in 10 (33%) patient, but no patients had prior systemic therapy. On first MR imaging (median 1.9, range 1.2 – 3.3 months), 26/28 patients had radiological disease control (RDC), with only 4 patients subsequently developing RDP at 5.8, 12.4, 15.3 and 20.7 months. Of the 27 patients presenting with symptoms at baseline, 22/27 patients achieved symptomatic response (median 4, range 1-39 weeks).
Conclusion
Early symptomatic improvement and RDC were reliable markers of durable treatment response. Given the high response rate and low incidence of acquired resistance, ICI should be considered earlier in the treatment paradigm in cSCC patients with LN-PNI, with an opportunity to avoid potentially disfiguring surgery.