Adjuvant cemiplimab significantly improves disease-free survival in patients with resected cutaneous squamous-cell carcinoma.
Adjuvant cemiplimab significantly improves disease-free survival in patients with resected cutaneous squamous-cell carcinoma at high risk for recurrence, a pivotal phase 3 randomised clinical trial has demonstrated.
The C-POST trial (NCT03969004) provides strong evidence supporting the integration of systemic immunotherapy into the adjuvant treatment paradigm for this patient population.
The results have been published in the New England Journal of Medicine.
“Adjuvant cemiplimab therapy led to longer disease-free survival than placebo among patients at high risk for recurrence of cutaneous squamous-cell carcinoma,” the authors concluded.
Patients with high-risk CSCC, particularly those with nodal involvement or aggressive local features, face substantial risk of recurrence despite surgery and postoperative radiotherapy.
Until now, no systemic adjuvant therapy had been conclusively proven to improve outcomes in this setting.
The multi-centre trial enrolled 415 patients with locally advanced or regionally metastatic CSCC who had undergone surgical resection and post-operative radiotherapy. Participants were stratified based on high-risk features, including:
- Nodal criteria: ≥3 involved lymph nodes or extracapsular extension with ≥20 mm nodal diameter.
- Non-nodal criteria: in-transit metastases, bone-invasive T4 lesions, perineural invasion, or recurrent tumours with additional risk features.
Patients were excluded if they had concurrent cancer (other than localised cutaneous squamous-cell carcinoma and certain low-risk diagnoses that were permitted according to the protocol); had received a solid-organ or stem-cell transplant previously; had clinically significant autoimmune disease or had received any previous immunotherapy for cutaneous squamous-cell carcinoma.
Patients were randomised in a 1:1 fashion to receive adjuvant cemiplimab (350 mg) or placebo, administered intravenously every three weeks for 12 weeks, followed by a dose increase to 700 mg administered every six weeks for up to 36 weeks (≤48 weeks total).
The primary end point was disease-free survival. Secondary end points included freedom from loco-regional recurrence, freedom from distant recurrence and safety.
Cemiplimab was superior to placebo with respect to disease-free survival (24 versus 65 events; hazard ratio for disease recurrence or death, 0.32; 95% confidence interval [CI], 0.20 to 0.51). The estimated 24-month disease-free survival was 87.1% (95% CI, 80.3 to 91.6) with cemiplimab and 64.1% (95% CI, 55.9 to 71.1) with placebo.
Cemiplimab led to lower risks of locoregional recurrence (9 events versus 40 with placebo; hazard ratio, 0.20; 9% CI, 0.09 to 0.40) and distant recurrence (10 versus 26 events; hazard ratio, 0.35; 95% CI, 0.17 to 0.72).
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Adverse events of grade 3 or higher occurred in 23.9% of the patients who received cemiplimab and in 14.2% of those who received placebo; discontinuation due to adverse events occurred in 9.8% and 1.5%, respectively.
These results suggested that cemiplimab, an anti–PD-1 monoclonal antibody, offered a substantial disease-free survival benefit in a population with historically limited treatment options beyond surgery and radiotherapy. While the safety profile is consistent with known immune-related toxicities, the overall tolerability supported its use in appropriately selected patients.
The authors acknowledged a limitation of the C-POST trial was that it was not designed to formally investigate differences in efficacy and safety between the two dose regimens in the trial.
“However, this trial provides randomised data regarding the standard administration regimen (every three weeks only) and a regimen with an extended administration interval (start at every three weeks, with a switch to every six weeks),” they wrote.
“The trial results indicated that both regimens prolonged disease-free survival and had similar safety profiles.”
