Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations

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Abstract

Background

The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure.

Methods

The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort.

Results

In the Zehir cohort, a significant difference was observed in median overall survival (mOS) between patients with NTRK MT and wild-type (WT) (mOS: 18.97 vs. 21.27 months, HR = 1.34, 95%CI 1.00-1.78; log-rank P = 0.047). In Samstein cohort, the mOS of NTRK mutant patients receiving ICIs has improved compared to WT patients (mOS: 21.00 vs. 11.00 months, log-rank P = 0.103). Notably, in subgroup analysis, ICIs significantly prolonged mOS in patients with NTRK3 MT than in WT patients (mOS: not available vs. 11.00 months, HR = 0.36, 95%CI 0.16–0.81; log-rank P = 0.009). Identical mOS between NTRK MT and WT patients receiving ICIs treatment (mOS: 13.24 vs. 13.50 months, log-rank P = 0.775) was observed in OAK/POPLAR cohort. Moreover, a similar programmed death ligand 1 (PD-L1) expression, but higher tumor mutational burden (TMB), blood TMB (bTMB) and enriched anti-tumor immunity were observed in NTRK MT compared to WT ( P < 0.05).

Conclusion

Taking high TMB or bTMB into consideration, patients with NTRK mutant NSCLC could benefit from ICIs treatment.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12890-023-02707-x.

Related collections

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Author and article information

Contributors

Xiuwen Wang: xiuwenwang12@sdu.edu.cn

Yanguo Liu: liuyanguo@sdu.edu.cn

Journal

Journal ID (nlm-ta): BMC Pulm Med

Journal ID (iso-abbrev): BMC Pulm Med

Title: BMC Pulmonary Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2466

Publication date (Electronic): 29 November 2023

Publication date PMC-release: 29 November 2023

Publication date Collection: 2023

Volume: 23

Electronic Location Identifier: 482

Affiliations

Department of Medical Oncology, Qilu Hospital of Shandong University, ( https://ror.org/056ef9489) 107 Wenhuaxi Road, Jinan, Shandong 250012 China

Article

Publisher ID: 2707

DOI: 10.1186/s12890-023-02707-x

PMC ID: 10688060

PubMed ID: 38031067

SO-VID: c0454698-9d9f-43d7-8352-a6cac4c9e360

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 8 May 2023

Date accepted : 12 October 2023

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: non-small cell lung cancer,ntrk family mutation,immune checkpoint inhibitors,tumor mutational burden,pd-l1 expression,overall survival

Data availability: