Adjuvant and Neoadjuvant PD‑1 Inhibitor Therapy for High‑Risk Melanoma

Overall Survival Benefit of Adjuvant PD‑1 Inhibitors

Adjuvant PD‑1 blockade with pembrolizumab or nivolumab improves overall survival in patients with completely resected high‑risk melanoma; the magnitude of benefit varies by stage and is most clearly demonstrated in stage III disease【1】【2】.

The American Society of Clinical Oncology (ASCO) strongly recommends a 52‑week course of either nivolumab 3 mg/kg every 2 weeks or pembrolizumab 200 mg every 3 weeks for all patients with resected stage IIIA‑D melanoma, irrespective of BRAF mutation status【1】【2】.
Both agents are supported by high‑quality evidence (level A) for improving recurrence‑free outcomes and are considered the standard of care【1】【2】.

For patients with BRAF‑mutant stage IIIA‑D melanoma, ASCO recommends any of the following for 52 weeks: nivolumab, pembrolizumab, or the targeted combination dabrafenib + trametinib【1】.
The three options are regarded as equally effective, with no preferential ranking; selection should be individualized based on patient tolerance for immune‑related versus targeted‑therapy toxicities【1】.

Patients with minimal sentinel‑node disease (<1 mm) were excluded from pivotal trials and generally have a better prognosis; ASCO advises cautious use of adjuvant therapy, emphasizing shared decision‑making regarding risk‑benefit and the option of observation【1】【2】.

For resected stage IIB‑C melanoma, ASCO recommends adjuvant nivolumab or pembrolizumab based on robust recurrence‑free survival benefits, despite overall‑survival data remaining immature【2】.
The recommendation is strong (grade A) because the magnitude of RFS improvement outweighs the lack of mature OS data【2】.

Long‑term immune‑related adverse events associated with PD‑1 inhibitors must be balanced against recurrence risk; ASCO guidelines provide detailed algorithms for monitoring and managing grade 3‑5 immune toxicities【2】.

The National Comprehensive Cancer Network (NCCN) now prefers neoadjuvant pembrolizumab over upfront surgery followed by adjuvant therapy for resectable stage III melanoma with clinically positive nodal disease【3】【4】.
In the SWOG S1801 trial, neoadjuvant pembrolizumab achieved a 2‑year event‑free survival of 72 % compared with 49 % for an adjuvant‑only strategy, demonstrating a clear efficacy advantage【3】【4】.
Neoadjuvant treatment enables pathologic response assessment, which can be used to tailor subsequent therapeutic decisions【4】.