Incidence of new keratinocyte cancers during pembrolizumab in resectable cutaneous squamous cell carcinoma: The De-Squamate study.

Abstract

9582 Background: Patients with advanced cutaneous squamous cell carcinoma (cSCC) or basal cell carcinoma (BCC) frequently develop new primary keratinocyte cancers (KCs) due to field cancerisation. Emerging data suggest immune checkpoint inhibitors (ICIs) may reduce this burden. We evaluated the incidence of new KCs in a prospective immunotherapy cohort. Methods: De-Squamate was a prospective phase II trial evaluating neoadjuvant pembrolizumab using a response-adapted management strategy in resectable cSCC. As part of protocol-mandated safety monitoring, all new primary KCs were prospectively recorded as adverse events. Events included histologically confirmed new cSCCs, BCCs, or other keratinocyte malignancies diagnosed and resected during or after treatment. Person-time was calculated for periods on pembrolizumab and off treatment. Incidence rates were calculated per person-year. Rate ratios were estimated using crude analyses and adjusted models accounting for within-patient clustering. Results: Among the 27 patients, 54 new KCs were recorded. Patients contributed 14.9 person-years on pembrolizumab and 33.4 person-years off treatment. KC incidence was lower during active therapy than after discontinuation (73.7 vs 143.6 per 100 person-years). The unadjusted rate ratio for new KC development off treatment versus on treatment was 1.95 (95% CI, 1.01–3.75). Adjusted analyses using negative-binomial modelling produced similar estimates (adjusted rate ratio 1.94; 95% CI, 0.64–5.89). Reductions were most pronounced for BCCs, with more modest effects observed for new primary cSCCs (table 1). Conclusions: In this prospective cohort, new KCs occurred at approximately twice the rate after discontinuation of pembrolizumab compared with during active therapy. These findings support the hypothesis that ICIs may suppress carcinogenesis within chronically damaged skin fields. Larger studies are needed to clarify the potential immunopreventative effect of ICIs in patients with field-driven KCs. Clinical trial information: NCT05025813 . Incidence of new keratinocyte cancers by treatment exposure. Outcome On Pembrolizumab Off Pembrolizumab (Follow-up) Unadjusted Rate Ratio† (95% CI) Adjusted Rate Ratio‡ (95% CI) Person-years 14.9 33.4 – – All keratinocyte cancers 11 events0.74 / PY 43 events1.29 / PY 1.95 (1.01–3.75) 1.94 (0.64–5.89) Cutaneous SCC (new primaries) 6 events0.40 / PY 10 events0.30 / PY 0.75* – Basal cell carcinoma 5 events0.34 / PY 38 events1.14 / PY 3.35* – †Off-treatment vs on-treatment. ‡Adjusted for patient-level clustering using negative-binomial model. *Crude comparison shown; formal adjusted estimates limited by small event numbers.