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Nonlinear association between body mass index and overall survival in advanced NSCLC patients treated with immune checkpoint blockade

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Abstract

Background

We investigated the association of body mass index (BMI) modeled as a continuous variable with survival outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI).

Methods

We performed a single-institution retrospective analysis of consecutively diagnosed locally advanced or metastatic NSCLC patients treated with single-agent ICI in the first line or recurrent setting. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and objective response rate (ORR). BMI was modeled using a four-knot restricted cubic spline. Multiple Cox regression was used for survival analysis.

Results

Two hundred patients were included (female 54%; never smoker 12%). Adenocarcinoma was the most common histology (61%). Median age was 67 years, median BMI was 25.9 kg/m2, and 65% of patients had Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1. On multivariable analysis, only BMI and ECOG PS were independently associated with OS (p < 0.01). Mortality risk decreased as the BMI increased from 20 to 30 kg/m2 (HR 0.49, 95% CI 0.28–0.84); however, it was reversed as the BMI surpassed ~ 30 kg/m2. Compared to ECOG PS ≥ 2, patients with ECOG PS of 0–1 had a longer OS (HR 0.42, 95% CI 0.28–0.63). Similar trends were observed with PFS and ORR, but the strength of the association was weaker.

Conclusion

We observed a nonlinear association between BMI and OS following treatment with ICI in advanced NSCLC. Risk of death increases at both extremes of BMI with a nadir that exists around 30 kg/m2.

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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.

Abbreviations

BMI:

Body mass index

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

ICI:

Immune checkpoint inhibitor(s)

IQR:

Interquartile range

NSCLC:

Non-small cell lung cancer

ORR:

Objective response rate

OS:

Overall survival

PFS:

Progression-free survival

PD-1:

Programmed death 1

PD-L1:

Programmed death ligand 1

PS:

Performance status

RECIST:

Response Evaluation Criteria in Solid Tumors

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Acknowledgements

Research reported in this study was supported by NIH grant P30CA077598 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1-TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA

    Aditya Jain, Shijia Zhang, Naomi Fujioka, Robert A. Kratzke, Manish R. Patel & Amit A. Kulkarni

  2. Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Ryan M. Shanley

Authors
  1. Aditya Jain
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  2. Shijia Zhang
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  3. Ryan M. Shanley
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  4. Naomi Fujioka
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  5. Robert A. Kratzke
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  6. Manish R. Patel
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  7. Amit A. Kulkarni
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by AK, SZ and RS. The first draft of the manuscript was written by AJ, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Amit A. Kulkarni.

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Conflict of interests

Dr. Patel serves on advisory board for Sanofi. Dr. Fujioka serves on advisory boards for Takeda Pharmaceutical and AstraZeneca. Dr. Kulkarni serves on advisory board of Genentech and has institutional grant funding from Astra Zeneca. Other authors declare they have no relevant financial or non-financial interests.

Ethics approval and consent

This was a retrospective study done in compliance with the statute laid down by the University of Minnesota Institutional Review Board (STUDY00018385). No ethics approval or informed consent from individual participants was deemed required.

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Jain, A., Zhang, S., Shanley, R.M. et al. Nonlinear association between body mass index and overall survival in advanced NSCLC patients treated with immune checkpoint blockade. Cancer Immunol Immunother 72, 1225–1232 (2023). https://doi.org/10.1007/s00262-022-03320-3

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  • DOI: https://doi.org/10.1007/s00262-022-03320-3

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