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Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations

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Abstract

Background

Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations.

Methods

From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan–Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable.

Results

A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events.

Conclusion

NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to appreciate all patients and their families for their cooperation and participation. Additionally, we are thankful to all research staff and co-investigators involved in this research.

Funding

The study was supported by the Medical Scientific Research Foundation of Zhejiang Province (No. 2022KY653), and sponsored by Zhejiang provincial program for the Cultivation of High-Level Innovative Health Talents (to Zhengbo Song).

Author information

Author notes

  1. Yanhua Wang, Jingwen Wei, and Manyi Xu have contributed equally to this work.

Authors and Affiliations

  1. The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310000, China

    Yanhua Wang, Manyi Xu, Jing Xiang & Yue Hao

  2. Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China

    Yanhua Wang, Jingwen Wei, Manyi Xu, Jing Xiang, Keda Shao & Zhengbo Song

  3. Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China

    Yanhua Wang, Jingwen Wei, Manyi Xu, Jing Xiang, Keda Shao, Yue Hao & Zhengbo Song

  4. Department of Clinical Trial, Zhejiang Cancer Hospital, No.1 East Banshan Road, Gongshu District, Hangzhou, 310022, Zhejiang, China

    Yue Hao & Zhengbo Song

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Contributions

ZS and YH designed and supervised the research. YW, JW, MX, JX and KS conducted the follow-up, data collection, and correlative analysis. YW, MX and YH provided support in data analysis and use of software. YW, JW, MX and KS provided data analysis. YW, MX and YH were involved in manuscript preparation and all the authors approved the final manuscript.

Corresponding authors

Correspondence to Yue Hao or Zhengbo Song.

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All authors declare no conflict of interest.

Ethics approval and consent to participate

Approval of the study protocol was obtained from Zhejiang Cancer Hospital Institutional Review Board Committee (approval number: IRB-2022-396). Individual consent for this retrospective analysis was waived.

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Not applicable.

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Individual consent for analysis was waived.

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Appendices

Appendix 1

See Fig.

Fig. 4
figure 4

The swimmer’s plot showing the PFS and OS for all NSCLC patients with PD-L1 positive. a The PFS for all NSCLC patients with PD-L1 positive; b the OS for all NSCLC patients with PD-L1 positive

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4.

Appendix 2

See Fig.

Fig. 5
figure 5

Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS). a PFS of three type patients with MET alterations (MET exon 14 skipping vs primary amplification vs secondary amplification: 9.2 vs 7.8 vs 3.4 months, p  = 0.645); b OS of three type patients with MET alterations (MET exon 14 skipping vs primary amplification vs secondary amplification: 16.7 vs 15.1 vs 10.8 months, p  = 0.493)

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5.

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Wang, Y., Wei, J., Xu, M. et al. Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03455-y

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