⚡A first for high-risk cutaneous SCC

Good morning — it’s Saturday, October 18, and we’re covering the first FDA-approved adjuvant immunotherapy for high-risk cutaneous SCC, one-year outcomes for the AviClear laser in acne, and more

First time reading? Sign up here.

Enjoying the newsletter? Share it with a friend or colleague — here’s the link.

P.S. You can send me feedback at [email protected]

The FDA has approved cemiplimab (Libtayo), a PD-1 checkpoint inhibitor, as the first immunotherapy for adjuvant use in high-risk cutaneous squamous-cell carcinoma (cSCC) following surgery and radiation.

The Phase 3 C-POST trial, published in NEJM, supported the approval. Investigators randomized 415 patients with local or regional high-risk cSCC to receive cemiplimab or placebo for up to 48 weeks. All patients had already undergone curative surgery followed by postoperative radiotherapy. High-risk features included nodal or non-nodal criteria.

Cemiplimab significantly improved disease-free survival compared with placebo, reducing the risk of recurrence or death by 68% (24 vs 65 events; HR 0.32; 95% CI, 0.20–0.51; P < 0.001).

At 24 months, disease-free survival was 87% with cemiplimab versus 64% with placebo. More patients also remained free of locoregional (95% vs 77%) and distant (94% vs 84%) recurrence.

In part 2 of the trial, patients initially on placebo who experienced recurrence could cross over to cemiplimab, with 43% achieving an objective radiographic response.

Although no overall survival benefit has yet emerged, follow-up is ongoing. At the April 2025 data cutoff, 33 deaths had occurred (15 vs 18; HR 0.78; 95% CI, 0.39–1.56).

Safety was consistent with known PD-1 class effects. Grade ≥3 adverse events were more frequent with cemiplimab (24% vs 14%), including one fatal case of myositis.

The results highlight the tension between using immunotherapy earlier to prevent recurrence and the added risks of toxicity and overtreatment in the absence of proven survival or quality-of-life benefit.

The FDA has already approved cemiplimab for unresectable or metastatic cSCC. European regulators are reviewing it for the adjuvant indication.

> Sebum-selective 1726 nm laser sustains acne clearance at one year: AviClear, the first FDA-cleared laser for mild-to-severe acne, showed durable one-year efficacy and high patient satisfaction, according to a study published in JAAD. The device targets sebaceous glands via selective photothermolysis at 1726 nm, a wavelength preferentially absorbed by sebum over water. In the prospective multicenter trial, 104 patients (Fitzpatrick II–VI) received three laser sessions spaced 2–5 weeks apart; 71 completed the 52-week follow-up. Of these, 66% achieved clear or almost-clear skin (IGA 0/1) at Week 52, up from 36% at Week 12. Lesion counts followed a similar trajectory. Inflammatory and non-inflammatory lesions fell by 79% and 58% at one year, compared with 56% and 25% at 12 weeks. Most patients (83%) were “satisfied” or “extremely satisfied” with treatment. Adverse events were mild and transient. Most involved erythema, edema, or short-term purging. No blistering, scarring, or pigmentary changes occurred. Limitations included the open-label design, small cohort, loss to follow-up, and lack of a control arm. See before-and-after photos illustrating efficacy here.

> First randomized trial shows taVNS improves erythema and flushing in rosacea: A double-blind randomized trial published in JAMA Dermatology is the first to evaluate transcutaneous auricular vagus nerve stimulation (taVNS) for erythematotelangiectatic rosacea (ETR). The noninvasive device delivers brief electrical impulses to the auricular branch of the vagus nerve. It has previously been explored in neurological and psychiatric conditions such as migraine and depression. Investigators randomized 72 patients with moderate ETR to taVNS or sham stimulation for 30 minutes daily over three weeks, followed by 24 weeks of treatment-free observation. At Week 3, mean Clinician’s Erythema Assessment scores (0–4 scale) improved from 3.0 to 1.6 with taVNS, but only from 2.9 to 2.5 with sham (mean difference –0.9; P < 0.001). Additionally, Global Flushing Severity Scale scores (0–10 scale) also declined from 7.1 to 2.7 with taVNS versus 6.5 to 5.1 with sham (Δ –2.36; P < 0.001). Notably, efficacy was sustained for 24 weeks after treatment ended. Benefits also extended to comorbidities: taVNS significantly reduced anxiety, depression, sleep disturbance, migraine, and fatigue scores compared with sham. Adverse events were uncommon and mild. The trial’s modest sample size and single-site design are limitations. Still, taVNS may represent a safe, low-cost, and non-invasive neuromodulatory option for ETR.

> Pumecitinib gel outperforms placebo and advances to Phase 3 in atopic dermatitis: A Phase 2b randomized trial, published in the BJD, found that pumecitinib gel 3% improved eczema severity in adults with atopic dermatitis. Investigators evaluated the topical JAK1/2 inhibitor in 277 adults with mild-to-moderate disease involving 3–20% body surface area. Patients applied pumecitinib gel 3% once daily (QD), twice daily (BID), or placebo, for 8 weeks. At the end of treatment, the mean percentage change in the Eczema Area and Severity Index (EASI) score was −84% with BID, −44% with QD, and −22% with placebo. Both active regimens outperformed placebo (P < 0.006), and BID was superior to QD (P < 0.001). Clinical improvement was evident after 1 week. However, there were no significant differences versus placebo in itch intensity (PP-NRS), patient-reported eczema severity (POEM), or quality-of-life (DLQI) scores. Safety was comparable between pumecitinib and placebo. The investigational drug has now advanced to Phase 3 evaluation.

Quizzes, cases, and perspectives to sharpen your clinical eye.

A retrospective case series described 13 patients with severe alopecia areata who had failed one to three JAK inhibitors but achieved at least 80% scalp hair coverage (SALT ≤ 20) after switching to a different JAK inhibitor. These findings suggest that nonresponse to one agent in this class may not necessarily predict lack of response to another (More)

In the open-label ARCADIA long-term extension study of 1,062 adolescents and adults with moderate-to-severe atopic dermatitis, nemolizumab maintained durable efficacy over two years. In observed case analyses, nearly 90% of patients achieved EASI 75 (≥75% improvement in disease severity). The IL-31 inhibitor was well tolerated with no new safety signals (More)

In a Phase 3 trial published in the BMJ, oral methylcobalamin halved the rate of grade ≥2 hand–foot syndrome compared with placebo in women with HER2-negative early breast cancer receiving adjuvant capecitabine (15% vs 29%). Methylcobalamin also reduced the need for capecitabine dose modifications. No treatment-specific adverse events were observed (More)

A split-body randomized trial of 14 women found that a high-intensity parallel-beam ultrasound-based skin tightening device was as effective as microfocused ultrasound with visualization for improving upper arm skin laxity after a single session. Procedure time, however, was significantly shorter with the parallel-beam system (23 vs 35 minutes; P < 0.001). Limitations included the small sample size and lack of long-term follow-up (More)