Activity and Safety of Immune Checkpoint Inhibitors in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis

Abstract

Immune-checkpoint inhibitors (ICIs) have widened the therapeutic scenario of different cancer types. Phase I/II trials have been designed to evaluate the role of ICIs both as single agents and in combination in neuroendocrine neoplasms (NENs), but as yet no randomized controlled phase III trials have been carried out. A systematic review and meta-analysis of studies published could help to reduce the biases of single-phase II trials. Efficacy data were obtained on 636 patients. Pooled percentages of the overall response rate (ORR) and disease control rate (DCR) were 10% (95% CI: 6–15%, I2 = 67%, p < 0.1) and 42% (95% CI: 28–56%, I2 = 93%, p < 0.1), respectively. Median progression-free survival (mPFS) was 4.1 months (95% CI 2.6–5.4; I2 = 96%, p < 0.1) and median overall survival (mOS) was 11 months (95% CI 4.8–21.1; I2 = 98%, p < 0.1). Among the ICIs used as single agents, the anti-PD1 toripalimab achieved the highest ORR. Combination regimens were superior to monotherapy, e.g., the ICI combination nivolumab + ipilimumab, and the ICI + anti-angiogenetic combination atezolizumab + bevacizumab, both of which warrant further investigation. Promising efficacy and a good safety profile of ICIs represent a valid opportunity for expanding the therapeutic landscape of NENs. Predictive biomarkers are needed to identify the most suitable candidates for these regimens.

Efficacy of Immune Checkpoint Inhibitors against Advanced or Metastatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis

“…A prior meta-analysis performed by Bongiovanni et al [57] investigated the activity of ICIs in NENs; however, their results were inconsistent from ours. In their study, the pooled ORR was 10%, and there was no significant difference in ORR between WD NENs (11%) and PD NENs (12%).…”

Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature

“…Microsatellite instability and high mutational load are pronounced in NECs, which suggest that immune checkpoint inhibitors are promising therapeutic option in NECs [ 76 ]. Phase 1/2 studies were conducted to evaluate the role of immune checkpoint inhibitors in NENs, which showed promising efficacy and manageable toxicity [ 77 ]. It is reasonable to assess the PD-L1 status of HR-negative HER2-negative NEC of the breast to consider the use of immune checkpoint inhibitors.…”

Medikamentöse Systemtherapie bei Neuroendokrinen Neoplasien des GastroEnteropankreatischen Systems

“…NET zeigen häufig einen niedrigen Tumor Mutational Burden (TMB) als potenziell negativen Prädiktor für eine Immuntherapie [60]. Bei NET G1/G2 des GEP-Systems zeigten Studien mit Pembrolizumab, Spartalizumab und Durvalumab plus Tremelimumab weitgehend negative Studienergebnisse [40,[60][61][62]. In der Monotherapie zeigte Toripalimab bisher das vielversprechendste Ergebnis [62]…”

“…Bei NET G1/G2 des GEP-Systems zeigten Studien mit Pembrolizumab, Spartalizumab und Durvalumab plus Tremelimumab weitgehend negative Studienergebnisse [40,[60][61][62]. In der Monotherapie zeigte Toripalimab bisher das vielversprechendste Ergebnis [62]…”