Considering adjuvant therapy for stage II melanoma

Cancer. 2020 Mar 15;126(6):1166-1174. doi: 10.1002/cncr.32585. Epub 2019 Dec 23.

Abstract

Melanoma is among the few cancers that demonstrate an increasing incidence over time. Simultaneously, this trend has been marked by an epidemiologic shift to earlier stage at diagnosis. Before 2011, treatment options were limited for patients with metastatic disease, and the median overall survival was less than 1 year. Since then, the field of melanoma therapeutics has undergone major changes. The use of anti-CTLA-4 and anti-PD1 immune checkpoint inhibitors and combination BRAF/MEK inhibitors for patients with BRAF V600 mutations has significantly extended survival and allowed some patients to remain in durable disease remission off therapy. It has now been confirmed that these classes of agents have a benefit for patients with stage III melanoma after surgical resection, and anti-PD1 and BRAF/MEK inhibitors are standards of care in this setting. Some patients with stage II disease (lymph node-negative; American Joint Committee on Cancer stage IIB and IIC) have worse melanoma-specific survival relative to some patients with stage III disease. Given these results, expanding the population of patients who are considered for adjuvant therapy to include those with stage II melanoma has become a priority, and randomized phase 3 clinical trials are underway. Moving into the future, the validation of patient risk-stratification and treatment-benefit prediction models will be important to improve the number needed to treat and limit exposure to toxicity in the large population of patients with early stage melanoma.

Keywords: BRAF; PD1; adjuvant therapy; immunotherapy; melanoma; pd-1; risk stratification; stage II; targeted therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Chemotherapy, Adjuvant
  • Humans
  • Immunotherapy / methods
  • Interferons / therapeutic use
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • Medical Illustration
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / pathology*
  • Melanoma / surgery
  • Neoplasm Recurrence, Local
  • Neoplasm Staging / methods*
  • Numbers Needed To Treat
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics
  • Risk Assessment
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interferons
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human