C-POST study of adjuvant cemiplimab for high-risk cutaneous squamous cell carcinoma (CSCC): Disease-free survival (DFS) analyses per high-risk criteria and per start time after radiotherapy.

Abstract

6083 Background: C-POST, a phase 3 trial (NCT03969004) in patients (pts) with high risk CSCC after surgery and radiotherapy (RT), demonstrated superior disease-free survival (DFS) for adjuvant cemiplimab (cemi) vs placebo (pbo) (HR, 0.32; P <0.0001); treatment discontinuation due to adverse events occurred in 9.8% vs 1.5% of pts (Rischin, et al. N Engl J Med . 2025). With approximately 6 months of additional follow-up, we present exploratory analyses of DFS per high-risk criteria and per the interval between completion of prior RT and study randomization (2-6 wk vs >6 wk). These additional analyses provide key data to understand the importance of risk factors and the impact of time post RT. Methods: Pts were randomized 1:1 (N=415) to adjuvant cemi or pbo (350 mg cemi or pbo Q3W for 12 wk, then 700 mg cemi or pbo Q6W for 36 wk). All pts had nodal high-risk disease (with extracapsular extension [ECE] and ≥1 node ≥20 mm, or ≥3 nodes regardless of ECE) and/or non-nodal high-risk disease (in-transit metastases, perineural invasion, T4 lesions, or recurrent CSCC with ≥1 other feature). Tumors could meet ≥1 high-risk criteria. Randomization occurred within 2-11 wk after completion of RT. Data cutoff was April 7, 2025. Results: Among 415 pts (209/206 cemi/pbo) randomized, the DFS HR was 0.35 (95% CI, 0.23-0.55) at a median follow-up of 30 months. The most common high-risk criterion was nodal ECE, present in 48.4% of pts (201/415). DFS was improved with cemi vs pbo across all high-risk features, including both nodal and non-nodal criteria (Table 1). A consistent benefit was observed regardless of whether the interval between prior RT completion and study randomization was 2-6 wk (DFS events, 17/117 [14.5%] vs 37/112 [33.0%]; HR, 0.39; 95% CI, 0.22-0.70) or >6 wk (DFS events, 12/91 [13.2%] vs 31/93 [33.3%]; HR, 0.36; 95% CI, 0.19-0.71). Conclusions: In this phase 3 study, adjuvant cemi demonstrated a DFS benefit vs pbo across all high-risk features and regardless of the interval between prior RT completion and randomization. Clinical trial information: NCT03969004 . DFS with cemi vs pbo: Analyses per high-risk criteria. Criteria a Met high risk criteria, n/N (%) DFS events in cemi arm, n/N (%) DFS events in pbo arm, n/N (%) DFS HR (95% CI) Nodal high risk ECE with ≥1 node ≥20 mm 201/415 (48.4) 14/105 (13.3) 27/96 (28.1) 0.44 (0.23-0.84) ≥3 nodes 71/415 (17.1) 7/34 (20.6) 18/37 (48.6) 0.34 (0.13-0.92) Non-nodal high risk In-transit metastases 41/415 (9.9) 2/20 (10.0) 9/21 (42.9) 0.07 (0.01-0.58) T4 lesion 33/415 (8.0) 6/17 (35.3) 5/16 (31.3) 0.58 (0.16-2.11) Perineural invasion 64/415 (15.4) 3/32 (9.4) 8/32 (25.0) 0.27 (0.07-1.04) Recurrent CSCC with ≥1 additional high-risk criteria 105/415 (25.3) 9/55 (16.4) 22/50 (44.0) 0.19 (0.08-0.45) a Tumors could meet ≥1 high-risk criteria.