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Immune-Checkpoint Inhibitors in Lung Neuroendocrine Tumors - A Systematic Review and Meta-Analysis.

Rita Carrilho Pichel1, Lavinia Benini2, Marco Romelli3

  • 1Department of Medical Oncology, Centro Hospitalar Universitário Do Porto, Unidade Local de Saúde de Santo António, Porto, Portugal.

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Summary

Immune-checkpoint inhibitors (ICIs) show promise for lung neuroendocrine tumors (NETs), particularly atypical carcinoids (ACs). Combination therapies, like temozolomide plus nivolumab, demonstrated higher response rates than monotherapy.

Keywords:
carcinoid tumorimmune-checkpoint inhibitorsimmunotherapyneuroendocrine tumorpulmonary

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Area of Science:

  • Oncology
  • Pulmonology
  • Immunotherapy

Background:

  • Lung neuroendocrine tumors (NETs), including typical and atypical carcinoids (ACs), represent a rare malignancy with limited therapeutic options.
  • Immune-checkpoint inhibitors (ICIs) are emerging as a potential treatment modality for various cancers, including lung NETs.

Purpose of the Study:

  • To systematically evaluate the efficacy of immune-checkpoint inhibitors (ICIs) in patients with lung neuroendocrine tumors (NETs).
  • To conduct a meta-analysis of objective response rates (ORR) for ICIs in lung NETs, including subgroup analyses by intervention type.

Main Methods:

  • A systematic review and meta-analysis of observational and interventional studies reporting ICI efficacy in lung NETs.
  • Searched Medline, Embase, Web of Science, and Cochrane Library up to May 2024, including 11 studies with 128 adult patients.
  • Excluded case reports and studies with insufficient data; assessed study quality and summarized results descriptively.

Main Results:

  • The overall objective response rate (ORR) for lung NETs treated with ICIs was 14.7%, with a significantly higher ORR of 44.4% for atypical carcinoids (ACs).
  • Combination therapies showed a trend towards higher ORR compared to ICI monotherapy (p=0.056).
  • The combination of temozolomide plus nivolumab achieved the highest ORR at 66.7%. Safety profiles were consistent with known ICI data.

Conclusions:

  • Immune-checkpoint inhibitors (ICIs) represent a promising therapeutic strategy for patients with lung neuroendocrine tumors (NETs), especially ACs.
  • Combination ICI regimens appear more effective than monotherapy, warranting further investigation in focused clinical trials.
  • Further research is needed to optimize ICI treatment for lung NETs and improve patient outcomes.