What to Do When Anti-PD-1 Therapy Fails in Patients With Melanoma

Oncology (Williston Park). 2019 Apr 15;33(4):141-8.

Abstract

Monotherapy with immune checkpoint inhibitors, specifically those targeting programmed death 1 (PD-1), has revolutionized the treatment of metastatic melanoma: approximately 40% of patients achieve a partial or complete response, many of which are durable. However, a subset of patients who initially respond to therapy will progress, leaving the majority of patients in need of an effective second-line approach. While some standard therapies exist, there has been robust interest in utilizing targeted immunotherapy combinations in this population to overcome primary or acquired resistance. Other approaches include treatment with anti-PD-1 agents beyond progression; targeting oligometastatic disease with surgery, radiation, and/or intratumor injections; and the use of other approved systemic therapies. This review summarizes the current available treatment strategies for patients with advanced melanoma when PD-1-directed therapy is not enough.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / therapeutic use*
  • CTLA-4 Antigen / antagonists & inhibitors*
  • Clinical Trials as Topic
  • Cytokines / therapeutic use
  • Disease Progression
  • Humans
  • Immunotherapy, Adoptive / methods
  • Ipilimumab
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Melanoma / therapy
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Neoplasm Metastasis
  • OX40 Ligand / immunology
  • Oncolytic Virotherapy / methods
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf
  • Radiotherapy, Adjuvant / methods
  • Receptors, Chimeric Antigen / drug effects
  • Toll-Like Receptors / agonists
  • Tumor Microenvironment / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • Cytokines
  • Ipilimumab
  • OX40 Ligand
  • Programmed Cell Death 1 Receptor
  • Receptors, Chimeric Antigen
  • Toll-Like Receptors
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • pembrolizumab
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinases