Efficacy of Checkpoint Inhibitors in Neuroendocrine Neoplasms: Mayo Clinic Experience

Pancreas. 2021 Apr 1;50(4):500-505. doi: 10.1097/MPA.0000000000001794.

Abstract

Objectives: Checkpoint inhibitors (CPIs) for low- and intermediate-grade neuroendocrine tumors (NETs) have been associated with limited efficacy; recent studies suggest CPIs may represent promising treatment for high-grade neuroendocrine neoplasms (NENs).

Methods: We examined 57 patients with NENs who were treated with CPIs to determine if NETs and neuroendocrine carcinomas (NECs) respond to immunotherapy.

Results: Patients with poorly differentiated NECs on CPI monotherapy had an objective response rate (ORR) of 0% and median progression-free survival (PFS) of 2.1 months (95% confidence interval [CI], 0.5-4.6). Patients with poorly differentiated NECs on dual CPI therapy had an ORR of 13% and PFS of 3.5 months (95% CI, 1.4-not reached [NR]). Patients with poorly differentiated NECs on CPI and cytotoxic therapy had an ORR of 36% with PFS of 4.2 months (95% CI, 1.6-NR). Well-differentiated grade 1 and 2 NETs on CPI monotherapy had an ORR of 25% with PFS NR. Well-differentiated grade 3 NETs had 0% ORR with a PFS of 2.9 months (95% CI, 1.4-4.2) on CPI monotherapy.

Conclusions: Checkpoint inhibitor therapy shows limited activity in patients with NENs. Future studies should identify biomarkers that can help identify patients who are likely responders to immunotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cytotoxins / administration & dosage
  • Cytotoxins / adverse effects
  • Female
  • Hospitals*
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Progression-Free Survival
  • Thyroiditis / chemically induced
  • Treatment Outcome
  • Young Adult

Substances

  • Cytotoxins
  • Immune Checkpoint Inhibitors