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

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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/m 2, 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/m 2 (HR 0.49, 95% CI 0.28-0.84); however, it was reversed as the BMI surpassed ~ 30 kg/m 2. 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/m 2.

Original languageEnglish (US)
Pages (from-to)1225-1232
Number of pages8
JournalCancer Immunology, Immunotherapy
Issue number5
StatePublished - May 2023

Bibliographical note

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.


  • BMI
  • Immune checkpoint inhibitors
  • Non-small cell lung cancer
  • Nonlinearity
  • Overall survival

PubMed: MeSH publication types

  • Journal Article


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