Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations
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 fam...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Pulmonary Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12890-023-02707-x |
| _version_ | 1827604547886907392 |
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| author | Xiaoling Shang Wengang Zhang Wenfei Han Handai Xia Ni Liu Xiuwen Wang Yanguo Liu |
| author_facet | Xiaoling Shang Wengang Zhang Wenfei Han Handai Xia Ni Liu Xiuwen Wang Yanguo Liu |
| author_sort | Xiaoling Shang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T06:01:39Z |
| format | Article |
| id | doaj.art-c5999d7da06d4b9985c66078545109ee |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-03-09T06:01:39Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-c5999d7da06d4b9985c66078545109ee2023-12-03T12:08:58ZengBMCBMC Pulmonary Medicine1471-24662023-11-0123111310.1186/s12890-023-02707-xEfficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutationsXiaoling Shang0Wengang Zhang1Wenfei Han2Handai Xia3Ni Liu4Xiuwen Wang5Yanguo Liu6Department of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityAbstract 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.https://doi.org/10.1186/s12890-023-02707-xNon-small cell lung cancerNTRK family mutationImmune checkpoint inhibitorsTumor mutational burdenPD-L1 expressionOverall survival |
| spellingShingle | Xiaoling Shang Wengang Zhang Wenfei Han Handai Xia Ni Liu Xiuwen Wang Yanguo Liu Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations BMC Pulmonary Medicine Non-small cell lung cancer NTRK family mutation Immune checkpoint inhibitors Tumor mutational burden PD-L1 expression Overall survival |
| title | Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations |
| title_full | Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations |
| title_fullStr | Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations |
| title_full_unstemmed | Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations |
| title_short | Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations |
| title_sort | efficacy of immune checkpoint inhibitors in non small cell lung cancer with ntrk family mutations |
| topic | Non-small cell lung cancer NTRK family mutation Immune checkpoint inhibitors Tumor mutational burden PD-L1 expression Overall survival |
| url | https://doi.org/10.1186/s12890-023-02707-x |
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