Primary immunotherapy monotherapy (PRIMO) in locally advanced cutaneous squamous cell carcinoma.

9585 Background: Neoadjuvant immunotherapy is a potential curative approach to patients with locally advanced cutaneous squamous cell carcinoma (cSCC) that offers an attractive alternative to traditional, often morbid surgery and/or radiation. In this study, we report our initial institutional experience treating patients with primary immunotherapy monotherapy (PRIMO) and reserving surgery or radiation for progression only. Methods: Patients with primary or recurrent locally advanced cSCC (AJCC 8 T3-4 or node positive or in-transit metastases) in whom surgical resection and/or definitive radiation were deemed excessively morbid or futile and were treated with PRIMO were included in an IRB-approved database. Patients were treated with IV cemiplimab (350mg q 3week) or pembrolizumab (200mg q3week or 400 q6week). Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) was scored according to iRECIST criteria. Kaplan Meier analysis was used to estimate overall survival (OS) and progression free survival (PFS). Univariate analysis (UVA) for PD was performed using Chi square for categorical variables and Kruskal-Wallis for continuous variables. Results: This study included 36 patients treated between 2017-2023, with a median age of 80 (61-96), and a median follow up of 13.5 months (8-20.5). Most patients had lesions on the head and neck (32; 88.9%), recurrent disease (26; 72.2%), and T3/4N0 disease (20; 55.6%), while 18 patients (50.0%) had nodal disease or in-transit metastases. Cemiplimab was used in 31 patients (86.1%) while pembrolizumab was used for 5 patients (13.9%). Twelve patients (33.3%) stopped PRIMO due to an immune-related adverse event (irAE). 1 and 2yr OS and 1 and 2yr PFS were 76%, 64%, 72% and 51%, respectively. Best initial response to PRIMO was a CR in 15 (41.7%), PR in 14 (38.9%), SD in 3 (8.3%) and PD in 4 (11.1%) patients. All 3 lesions (100%) with SD and 3/14 lesions (21.4%) with PR ultimately progressed with a median duration of response of only 3 months (2.0-6.8), while all 15 lesions (100%) with a CR and 11/14 lesions with a PR (78.5%) remain controlled at last follow up with a median duration of response of 15.5 months (8.8 – 23.3) (p<0.001). The median duration of months of ongoing response after the completion of PRIMO was 11 (0-57). The median number of treatment cycles was 14 (2-36) in all patients, and 16 (2-36) in the 26 patients that did not progress. The only variable significantly associated with PD on UVA was the lack of irAE; 10/26 (38.5%) patients who did not have an irAE experienced PD, while 0/12 patients (0%) who had an irAE experienced PD (p=0.035). Conclusions: The use of PRIMO for locally advanced cSCC produces impressive response rates that appear durable without any additional therapy. This attractive alternative to the emerging neoadjuvant paradigm deserves prospective validation with longer term follow up.