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

Lung neuroendocrine tumors (NETs) are well-differentiated neuroendocrine neoplasms of lung origin, including typical and atypical carcinoids (ACs). Therapeutic options for this rare disease are limited in daily clinical practice. Immune-checkpoint inhibitors (ICIs) are under clinical investigation. Here, we report a systematic reappraisal about ICIs results in lung NETs. We reviewed articles on observational or interventional studies that reported efficacy data of ICIs in lung NETs. Case reports and studies with insufficient data were excluded from the analysis. We searched the electronic databases Medline, Embase, Web of Science, and Cochrane Library up to May 2024. Two investigators independently screened the identified records and assessed studies quality. We summarized the results descriptively and in a meta-analysis of ORR according to the type of intervention. The search retrieved 1344 records. After selection, we included 11 studies in the meta-analysis of ORR, with a total of 128 adult patients with lung NET (25% ACs) that were progressing after at least one line of systemic therapy, including treatment with somatostatin analogs. Ten studies were Phase II, and 1 study was phase Ib. The summary ORR was 14.7% (95% CI, 5.8-32.2), 44.4% (27.2-63.1) for ACs. Subgroup analysis by intervention types showed a trend for lower ORR of lung NETs treated with ICI monotherapy (ORR: 2.7%; 0.0-63.7) compared with combinations (p-value: 0.056). The combination of temozolomide plus nivolumab showed the highest ORR (66.7%; 33.3-88.9). The median OS (reported in 2 studies) was not reached. Safety was consistent with historical data of ICIs. Our work suggests that ICIs are a promising treatment for patients with lung NETs, especially ACs, and warrant further investigation in more focused studies.