Adjuvant cemiplimab prolongs DFS in cutaneous SCC

In the phase III C-POST trial, adjuvant cemiplimab prolongs disease-free survival (DFS) in individuals at high risk for recurrence of cutaneous squamous cell carcinoma (cSCC).

“In this primary analysis … DFS was significantly longer with adjuvant cemiplimab vs placebo in patients at high risk for recurrence of cSCC after definitive local therapy,” said the researchers.

A significant DFS benefit was observed with cemiplimab vs placebo (median not reached vs 49.4 months; HR for disease recurrence or death, 0.32; p<0.001). The estimated 24-month DFS was 87.1 percent and 64.1 percent in the respective cemiplimab and placebo arms. [N Engl J Med 2025 Aug 21;393:774-785]

“The Kaplan-Meier curves for DFS diverged early, with continued separation throughout the follow-up period, thus indicating a rapid and sustained clinical benefit with cemiplimab,” said the researchers.

A consistent pattern favouring cemiplimab over placebo was observed across all prespecified subgroups, with HRs ranging from 0.18 to 0.51. Of note, the DFS benefit was sustained regardless of tumoural PD-L1 status (8 vs 16 events; HR, 0.32 [PD-L1 TPS* <1 percent] and 14 vs 45 events; HR, 0.28 [PD-L1 TPS ≥1 percent]).

The cemiplimab arm also had a higher rate of freedom from locoregional recurrence (LRR; 94.6 percent vs 76.7 percent) and distant recurrence (DR; 94.3 percent vs 83.8 percent), and thus fewer LRRs (n=9 vs 40; HR, 0.20) and DRs (n=10 vs 26; HR, 0.35) than the placebo arm at 24 months.

According to the researchers, LRRs are notable events for patients with cSCC because they are associated with considerable risks of disease and death.

There were 25 deaths at data cutoff: 12 (n=4 [cemiplimab] and 8 [placebo]) due to disease progression and 13 (n=8 and 5, respectively) due to other causes. Overall survival at 2 years was 94.8 percent and 92.3 percent for cemiplimab and placebo, respectively.

Safety profile

There were more cemiplimab than placebo recipients who reported grade ≥3 adverse events (AEs) due to any cause (23.9 percent vs 14.2 percent). About 10 percent of cemiplimab recipients had grade ≥3 AEs that the investigators considered treatment-related. Two patients in each arm experienced AEs (regardless of attribution) that led to death. One cemiplimab recipient died due to myositis, and this was deemed treatment-related.

The cemiplimab arm also had a higher rate of discontinuation due to AEs than the placebo arm (9.8 percent vs 1.5 percent). About a quarter (22.9 percent) of cemiplimab recipients reported immune-related AEs (irAEs; 7.3 percent grade ≥3 events); the corresponding rate in the placebo arm was 6.4 percent (no grade ≥3 events). No new irAEs were observed.

The most common AEs with cemiplimab were fatigue (22 percent), pruritus (16.1 percent), rash (16.1 percent), and diarrhoea (15.6 percent).

Post-treatment recurrence

“Surgery with curative intent is the centrepiece of the clinical management of cSCC, with cure in ~95 percent of patients. However, a subset of patients with cSCC have disease recurrence, either locoregional or distant, after undergoing surgery and receiving adjuvant radiotherapy (RT),” the investigators pointed out.

The study enrolled individuals with local or regional cSCC who had completed both curative-intent surgery and postop RT (or concurrent chemoradiotherapy). A total of 415 patients (median age 71 years, 83.9 percent men) were randomized 1:1 to IV cemiplimab 350 mg or placebo Q3W for 12 weeks, followed by cemiplimab 700 mg Q6W for up to 36 weeks . About 83 percent had primary cSCC of the head and neck. Nearly 60 percent had high-risk nodal disease.

The researchers underlined the importance of individualized decision-making to determine whether a patient with high-risk cSCC should be treated in the context of adjuvant therapy or wait until disease recurrence occurs before initiating immunotherapy.

“Because anti-PD-1 therapy provides durable responses in <50 percent of patients in the context of advanced cSCC, the ability of adjuvant cemiplimab to reduce the risk of cSCC recurrence is clinically meaningful for patients at high risk for recurrence,” they concluded.