Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis

Br J Cancer. 2021 Feb;124(3):574-580. doi: 10.1038/s41416-020-01121-y. Epub 2020 Oct 22.


Background: Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown.

Methods: Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included. Disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcomes were examined.

Results: Eighty-five patients developed recurrent melanoma; nineteen (22%) during adjuvant TT. Median time to first recurrence was 18 months and median follow-up from first recurrence was 31 months. Fifty-eight (68%) patients received immunotherapy (IT) or TT as 1st line systemic therapy at either first or subsequent recurrence and had disease that was assessable for response. Response to anti-PD-1 (±trial agent), combination ipilimumab-nivolumab, TT rechallenge and ipilimumab monotherapy was 63%, 62% 25% and 10% respectively. Twenty-eight (33%) patients had died at census, all from melanoma. Two-year OS was 84% for anti-PD-1 therapy (±trial agent), 92% for combination ipilimumab and nivolumab, 49% for TT and 45% for ipilimumab monotherapy (p = 0.028).

Conclusions: Patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 based therapy and have outcomes similar to those seen when first line anti-PD-1 therapy is used in stage IV melanoma.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chemotherapy, Adjuvant
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy
  • Ipilimumab / administration & dosage
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / therapy
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Nivolumab / administration & dosage
  • Proto-Oncogene Proteins B-raf / genetics
  • Radiotherapy, Adjuvant
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / mortality
  • Skin Neoplasms / therapy
  • Young Adult


  • Immune Checkpoint Inhibitors
  • Ipilimumab
  • Nivolumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf