肺神经内分泌肿瘤中的免疫检查点抑制剂——一项系统评价与荟萃分析

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

作者信息

Pichel Rita Carrilho, Benini Lavinia, Romelli Marco, Gandini Sara, Gervaso Lorenzo, Valente Monica, De Sousa Maria João, Araújo Alexandra, Araújo António, Di Giacomo Anna Maria, Fazio Nicola

机构信息

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

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.

出版信息

Onco Targets Ther. 2025 Jul 31;18:833-843. doi: 10.2147/OTT.S515194. eCollection 2025.

Abstract

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.

摘要

肺神经内分泌肿瘤(NETs)是起源于肺的高分化神经内分泌肿瘤,包括典型类癌和非典型类癌(ACs)。在日常临床实践中,这种罕见疾病的治疗选择有限。免疫检查点抑制剂(ICIs)正在进行临床研究。在此,我们报告了关于ICIs治疗肺NETs结果的系统重新评估。我们回顾了关于观察性或干预性研究的文章,这些研究报告了ICIs在肺NETs中的疗效数据。病例报告和数据不足的研究被排除在分析之外。我们检索了截至2024年5月的电子数据库Medline、Embase、科学网和考科蓝图书馆。两名研究人员独立筛选已识别的记录并评估研究质量。我们根据干预类型对结果进行了描述性总结,并对客观缓解率(ORR)进行了荟萃分析。检索到1344条记录。经过筛选,我们在ORR的荟萃分析中纳入了11项研究,共有128例成年肺NET患者(25%为ACs),这些患者在至少一线全身治疗(包括使用生长抑素类似物治疗)后病情进展。10项研究为II期,1项研究为Ib期。汇总的ORR为14.7%(95%CI,5.8 - 32.2),ACs为44.4%(27.2 - 63.1)。按干预类型进行的亚组分析显示,与联合治疗相比,ICI单药治疗的肺NETs的ORR有降低趋势(ORR:2.7%;0.0 - 63.7)(p值:0.056)。替莫唑胺联合纳武单抗的ORR最高(66.7%;33.3 - 88.9)。中位总生存期(2项研究报告)未达到。安全性与ICIs的历史数据一致。我们的研究表明,ICIs对于肺NET患者,尤其是ACs患者,是一种有前景的治疗方法,值得在更有针对性的研究中进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/385b/12325105/8e0397e86ded/OTT-18-833-g0001.jpg

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