TOPLINE

Adjuvant anti-PD-1 therapy was associated with higher 5-year overall survival (OS) in patients with resected stage III melanoma than in matched untreated patients. However, at the population level, no survival difference was observed after adjuvant anti-PD-1 introduction in Denmark.

METHODOLOGY

• Researchers conducted a retrospective, nationwide cohort study comparing patients aged 18 years or older with resected stage IIIA-D cutaneous melanoma diagnosed before (pre-cohort: June 2016 to May 2018; n = 450) and after (post-cohort: January 2019 to December 2020; n = 552) the implementation of adjuvant anti-PD-1 therapy in Denmark.
• A total of 297 patients (53.8%) in the post-cohort received adjuvant anti-PD-1 (nivolumab 6 mg/kg every 4 weeks or pembrolizumab 4 mg/kg every 6 weeks) for up to 1 year.
• Propensity score matching was performed to compare adjuvant anti-PD-1-treated patients from the post-cohort (n = 279) with patients from the pre-cohort (n = 279), adjusting for age, sex, Charlson Comorbidity Index, Breslow thickness, ulceration, American Joint Committee on Cancer staging system eighth edition substage, N-category, and N-subclass.
• Primary endpoints were 5-year OS and melanoma-specific mortality, with a median follow-up duration exceeding 5 years in both cohorts.

TAKEAWAY

• At the population level, no difference in 5-year OS or melanoma-specific mortality was seen between the total pre- and post-cohorts.
• In the matched analysis, adjuvant anti-PD-1 was associated with higher 5-year OS (80.3% in treated patients vs 71.7% in untreated patients; hazard ratio [HR], 0.67; log-rank P = .022), corresponding to an absolute difference of 8.6 percentage points.
• Results for 5-year melanoma-specific mortality in the matched analysis pointed in the same direction but were inconclusive (16.6% in treated patients vs 20.8% in untreated patients; HR, 0.77; P = .24).
• Among matched patients with clinically occult nodal disease (sentinel node metastases only), results were also inconclusive for 5-year OS (HR, 0.70; 95% CI, 0.46-1.06; log-rank P = .094) and melanoma-specific mortality (HR, 0.68; 95% CI, 0.42-1.08; P = .11).
• Other-cause mortality was significantly lower in treated patients, raising concerns for residual confounding.

IN PRACTICE

"The uncertainty in disease-specific outcomes and limited power precludes any firm conclusions. Mature trial data and extended real-world studies are needed to fully evaluate the survival impact of adjuvant anti-PD-1 therapy," the authors wrote. "Until then, carefully individualized adjuvant treatment decisions are of particular importance," they added.

SOURCE

The study was led by Marie B. Weitemeyer, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark. It was published online on August 31, 2026, in the Journal of the European Academy of Dermatology & Venereology.

LIMITATIONS

The observed survival outcomes may have reflected residual confounding and limited statistical power. Differences in metastatic treatment patterns between the two cohorts could have masked or exaggerated adjuvant therapy effects. Additionally, surgical treatment and surveillance protocols evolved during the study period, which could have introduced surveillance bias.

DISCLOSURES

This study was supported by grants from the Danish Cancer Society, Danish Cancer Research Foundation, Herlev and Gentofte Hospital, and other foundations. Weitemeyer reported receiving research grants — including travel and conference support — from SkylineDx, all unrelated to the submitted work, and serving as the secretary for the Danish Melanoma Group. Several authors reported receiving honoraria, consulting fees, research support, or travel support from pharmaceutical companies including Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, and others. Multiple authors reported being members of the Danish Melanoma Group or Danish Medicines Council melanoma expert committee. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.