Early burden reduction after two doses of cemiplimab in advanced non-melanoma skin cancer.

Abstract

9583 Background: Advanced non-melanoma skin cancers (NMSC) frequently impose a high disease-related burden—severe pain, ulceration, intensive wound care—particularly in older and frail patients (pts). While cemiplimab has established antitumor activity, early pts-centered clinical benefit prior to first radiologic evaluation is under-described in routine practice. We quantified early changes in key burden domains after 2 infusions. Methods: A retrospective analysis was performed in a real-world cohort of pts with locally advanced/metastatic NMSC treated with cemiplimab. Assessments at T0 (≤7 days pre-treatment) and T1 (day 35–49; after 2 infusions). Pain intensity (0–10 Numeric Rating Scale, NRS), wound-care frequency (dressing changes/week), and analgesic exposure were extracted from structured clinical/nursing documentation; opioid exposure was quantified as daily morphine milligram equivalents (MME) using standard conversion. Primary endpoint: meaningful early pain benefit at T1 (≥2-point NRS decrease without analgesic escalation). Other endpoints: opioid de-escalation, wound-care reduction (≥2 fewer dressing changes/week), and a pragmatic early-burden composite (improvement in ≥2 of: primary pain benefit; opioid de-escalation; wound-care reduction). Paired Wilcoxon signed-rank and McNemar tests were used. Infection status summarized. Confounding-restricted sensitivity analyses excluded pts receiving RT/surgery within 8 weeks of treatment initiation. Results: 53 pts included; median age 80yr (IQR 71–88); 81% locally advanced disease; ECOG 0–1 56%. Baseline burden: median pain NRS 7 (IQR 6–8); baseline opioid use 60%; wound-care frequency median 4/week; ulceration G≥2 64.2%. At T1 median pain NRS improved to 3 (IQR 2–4) (median Δ −3; p<0.001). The primary endpoint was achieved in 83% (44/53; 95% CI 70.8-90.8). The proportion of pts receiving opioids decreased from 60% (32/53) at T0 to 22.6% (12/53) at T1 (p=0.00024). Median daily MME decreased from 20 mg (IQR 0–33) to 0 mg (IQR 0–14) (p<0.001). Among baseline opioid users (n=32), 100% reduced dose and/or discontinued opioids by T1 (32/32; 95% CI 88.6–100). Wound-care frequency decreased from median 4/week to 1/week (p<0.001), with wound-care reduction ≥2/week in 67.9% (36/53). The pragmatic early-burden composite was met in 79.2% (42/53). At first radiologic evaluation (median 91 days), RECIST evaluable in 51 pts; ORR was 76.4% (39/51) and disease control was 96.2% (50/52). Any immune-related AE occurred in 34% (18/53), with G≥3 in 1.9% (1/53). Infection decreased from 43% to 3.8% at T1. Conclusions: In an elderly, frail real-world population with NMSC and high supportive-care needs, cemiplimab was associated with rapid, meaningful early clinical benefit after two doses. Early burden endpoints may complement radiologic response to better capture patient-centered benefit and inform supportive-care planning in routine pathways.