Immunotherapy Response in Cutaneous Squamous Cell Carcinoma Patients with Cranial Nerve Involvement

Purpose/Objective(s) Immunotherapy (IO) with cemiplimab or pembrolizumab is approved for treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC). There is evidence of objective response to these anti-PD-1 agents in locally advanced cSCC. Cranial nerve (CN) involvement is seen in less than 5% of cSCC and is a poor prognostic factor. Radiotherapy (RT) can be used for locally advanced cSCC, however comprehensive delineation and eradication of perineural invasion can be challenging. To our knowledge, there are no published studies indicating how patients with CN involvement respond to IO. Materials/Methods Patients were identified and retrospectively reviewed under an Institutional Review Board approved protocol at a tertiary care center. Selection criteria included histologically proven locally advanced cSCC of the head and neck cancer with CN involvement treated with IO. Results A total of 8 patients met inclusion criteria; demographic, disease, and treatment characteristics are summarized in Table 1. Most patients were men, with a median age at diagnosis of 74 years and had a median follow-up of 8.4 months. All received cemiplimab 350 mg intravenously every 3 weeks; 1 patient was initially treated with pembrolizumab, then transitioned to cemiplimab. 2 patients received IO for recurrence of previously diagnosed locally advanced cSCC, 1 of which had prior treatment with cetuximab and RT. 6 patients presented with CN involvement at diagnosis, and the additional 2 at time of recurrence after previous non-IO therapy. 1 patient treated with IO was immunosuppressed due to CLL and also had nodal involvement. 4 patients received RT prior to IO, and 1 patient received stereotactic radiosurgery (SRS) concurrent with IO. 3 patients never received RT and all had clinical benefit with IO: 2 having stable disease (SD) and 1 partial response (PR). Overall, 4 patients had PR, 2 SD and 2 progressive disease (PD) as best response. 5 patients are alive at last follow up, 1 completed a full year of IO and is currently off treatment, and 4 remain on IO treatment. Conclusion In this limited cohort of patients with locally advanced cSCC with CN involvement, IO has shown clinical benefit in 75% of the cases. All patients treated with IO alone demonstrated a clinical response, indicating IO can be an effective monotherapy. Given the challenges of RT with extensive perineural invasion, RT can be reserved in the event of local failure after IO. Immunotherapy (IO) with cemiplimab or pembrolizumab is approved for treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC). There is evidence of objective response to these anti-PD-1 agents in locally advanced cSCC. Cranial nerve (CN) involvement is seen in less than 5% of cSCC and is a poor prognostic factor. Radiotherapy (RT) can be used for locally advanced cSCC, however comprehensive delineation and eradication of perineural invasion can be challenging. To our knowledge, there are no published studies indicating how patients with CN involvement respond to IO. Patients were identified and retrospectively reviewed under an Institutional Review Board approved protocol at a tertiary care center. Selection criteria included histologically proven locally advanced cSCC of the head and neck cancer with CN involvement treated with IO. A total of 8 patients met inclusion criteria; demographic, disease, and treatment characteristics are summarized in Table 1. Most patients were men, with a median age at diagnosis of 74 years and had a median follow-up of 8.4 months. All received cemiplimab 350 mg intravenously every 3 weeks; 1 patient was initially treated with pembrolizumab, then transitioned to cemiplimab. 2 patients received IO for recurrence of previously diagnosed locally advanced cSCC, 1 of which had prior treatment with cetuximab and RT. 6 patients presented with CN involvement at diagnosis, and the additional 2 at time of recurrence after previous non-IO therapy. 1 patient treated with IO was immunosuppressed due to CLL and also had nodal involvement. 4 patients received RT prior to IO, and 1 patient received stereotactic radiosurgery (SRS) concurrent with IO. 3 patients never received RT and all had clinical benefit with IO: 2 having stable disease (SD) and 1 partial response (PR). Overall, 4 patients had PR, 2 SD and 2 progressive disease (PD) as best response. 5 patients are alive at last follow up, 1 completed a full year of IO and is currently off treatment, and 4 remain on IO treatment. In this limited cohort of patients with locally advanced cSCC with CN involvement, IO has shown clinical benefit in 75% of the cases. All patients treated with IO alone demonstrated a clinical response, indicating IO can be an effective monotherapy. Given the challenges of RT with extensive perineural invasion, RT can be reserved in the event of local failure after IO.