Treatment of resectable stage III-IV melanoma with both neoadjuvant and adjuvant (periadjuvant) pembrolizumab may provide better outcomes than adjuvant pembrolizumab alone, according to study results published in The New England Journal of Medicine.

Patients who received periadjuvant pembrolizumab had significantly longer event-free survival (EFS) than patients in the adjuvant group, with similar toxicity, researchers observed.

This open-label, phase 2 trial ( Identifier: NCT03698019) included 313 patients with resectable stage IIIB-IVC melanoma. They were randomly assigned to receive 3 doses of neoadjuvant pembrolizumab and 15 doses of adjuvant pembrolizumab (n=154) or 18 doses of adjuvant pembrolizumab only (n=159). 

Continue Reading

At a median follow-up of 14.7 months, EFS was significantly longer in the periadjuvant group (P =.004). The 2-year EFS rate was 72% in the periadjuvant group and 49% in the adjuvant-only group. EFS at 2 years favored periadjuvant therapy across all subgroups.  

In the periadjuvant group, 50 patients completed all adjuvant treatment cycles, and none of them had disease recurrence. In the adjuvant group, 38 patients completed all adjuvant treatment cycles, and 4 (11%) had disease recurrence.

In both treatment groups, most patients underwent definitive surgery — 88% in the periadjuvant group and 95% in the adjuvant group. Ten patients in the periadjuvant group were still receiving neoadjuvant pembrolizumab at the time of analysis. 

Other reasons that patients in the periadjuvant group did not undergo surgery included disease progression (n=12), consent withdrawal (n=2), toxicity (n=1), and coexisting conditions (n=1). One additional patient declined surgery after achieving a clinical complete response and remained in response at 31.5 months of follow-up.

Reasons for not undergoing surgery in the adjuvant-only group included consent withdrawal (n=7) and scheduling issues (n=1).

There were 19 grade 3-4 adverse events (AEs) attributed to neoadjuvant therapy and 7 grade 3-4 AEs attributed to adjuvant therapy in the periadjuvant group. There were 11 grade 3-4 AEs attributed to adjuvant therapy in the adjuvant-alone group. There were no deaths attributed to pembrolizumab in either group.

“Our trial shows that the timing of administration of an immune checkpoint inhibitor relative to surgery can have a large effect on patient outcomes, even though the same systemic therapy was given to both trial groups,” the researchers concluded.

Disclosures: This study was supported in part by Merck Sharp and Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Patel SP, Othus M, Chen Y, et al. Neoadjuvant–adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med. Published online March 2, 2023. doi:10.1056/NEJMoa2211437