Journal
CANCERS
Volume 14, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cancers14030794
Keywords
checkpoint inhibitors; immunotherapy; neuroendocrine neoplasm; treatment efficacy
Categories
Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [2021R1C1C1010138]
- National Research Foundation of Korea [2021R1C1C1010138] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This meta-analysis evaluated the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic neuroendocrine neoplasms (NENs). It found that the response to ICIs varied depending on the primary tumor site, tumor differentiation, and drug regimen. Poorly differentiated NENs showed a better overall response rate but had a negative impact on survival.
Simple Summary Neuroendocrine neoplasms (NENs) are relatively rare neoplasms, but their incidence is rising. Despite the recent understanding of and advances in the treatment of NENs, the clinical outcomes of patients with NENs, especially high-grade NENs, are poor. This meta-analysis was conducted to systematically evaluate the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic NENs. In 10 studies with 464 patients, the pooled overall response rate was 15.5% (95% confidence interval, 9.5-24.3%), but the response differed according to the primary tumor site, tumor differentiation, and drug regimen. Poorly differentiated NENs consistently showed a better overall response rate than well-differentiated NENs in multiple sensitivity analyses, suggesting that different expression of immune checkpoints and tumor mutational burden may influence the treatment efficacy of ICIs for advanced or metastatic NENs. The variation in treatment efficacy of ICIs according to tumor differentiation and drug regimen should be considered for patient-tailored management. We performed a systematic review and meta-analysis of the treatment efficacy of immune checkpoint inhibitors (ICIs) in advanced/metastatic neuroendocrine neoplasms (NENs). MEDLINE and EMBASE were searched to identify studies that provide data on treatment response and/or survival outcomes of advanced/metastatic NEN patients treated with ICIs. The overall response rate (ORR) was pooled using a random-effects model. Meta-regression was performed to explore factors influencing the ORR. Individual patient data (IPD) meta-analysis of survival was performed using stratified Cox regression. Ten studies (464 patients) were included. The overall pooled ORR was 15.5% (95% confidence interval (CI), 9.5-24.3%), and it varied according to the primary site (thoracic, 24.7%; gastro-entero-pancreatic, 9.5%), tumor differentiation (poorly differentiated, 22.7%; well-differentiated, 10.4%), and drug regimen (combination, 25.3%; monotherapy, 10.1%). All these variables significantly influenced the ORR. Tumor differentiation was associated with both overall survival and progression-free survival (hazard ratio of poorly differentiated tumors, 4.2 (95% CI, 2.0-8.7) and 2.6 (95% CI, 1.6-4.4), respectively). Thus, the treatment efficacy of ICIs for advanced/metastatic NENs varied according to primary site, tumor differentiation, and drug regimen. Poorly differentiated NENs showed a better ORR than well-differentiated NENs but had a negative impact on survival.
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