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Accepted for/Published in: JMIR Cancer

Date Submitted: Jul 30, 2024
Date Accepted: Jul 22, 2025

The final, peer-reviewed published version of this preprint can be found here:

Impact of Immune Checkpoint Inhibitors on Second Primary Cancer Risk in Patients With Metastatic Lung Cancer Using Real-World Data From the TriNetX Network: Retrospective Cohort Study

Heudel P, Hernandez G, Denquin O, Crochet H, Blay JY

Impact of Immune Checkpoint Inhibitors on Second Primary Cancer Risk in Patients With Metastatic Lung Cancer Using Real-World Data From the TriNetX Network: Retrospective Cohort Study

JMIR Cancer 2025;11:e64900

DOI: 10.2196/64900

PMID: 41118671

PMCID: 12539796

Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

Real-World Evidence from the TriNetX Network: Assessing Immunotherapy's Impact on Second Primary Cancer Risk in Metastatic Lung Cancer

  • Pierre Heudel; 
  • Gema Hernandez; 
  • Olivier Denquin; 
  • Hugo Crochet; 
  • Jean-Yves Blay

ABSTRACT

Background:

Lung cancer survivors are at high risk of developing a second primary cancer (SPC). This study investigated the impact of immune checkpoint inhibitors (ICIs) on the risk to develop a SPC in a large cohort of metastatic lung cancer patients.

Objective:

This study investigated the impact of immune checkpoint inhibitors (ICIs) on the risk to develop a SPC in a large cohort of metastatic lung cancer patients.

Methods:

Using a retrospective cohort from the TriNetX Global Collaborative research network, the study analyzed the incidence of SPC in metastatic lung cancer (MLC) patients treated with ICIs against those who were not. Propensity score matching and Kaplan-Meier to assess the effect of ICIs on the development of SPCs.

Results:

The study analyzed 2,844 MLC patients, with 685 receiving ICIs and 2,157 not receiving ICIs. Post-propensity score matching, each cohort included 685 patients. The 5-year analysis revealed a lower incidence of SPCs in the ICI group (1.5%) compared to the non-ICI group (4.2%), with a Hazard Ratio (HR) of 0.49 (95%CI [0.24-1.01]) indicating a reduced risk. Treatment with ICIs was associated with a significant risk reduction of SPC or death (HR=0.78; 95%CI [0.62-0.89]).

Conclusions:

ICIs reduce the risk of SPCs in metastatic lung cancer patients. Despite limitations, the study confirms the preventive role of ICIs and the importance of real-world data to identify novel paradigm changing strategies. Clinical Trial: Not applicable


 Citation

Please cite as:

Heudel P, Hernandez G, Denquin O, Crochet H, Blay JY

Impact of Immune Checkpoint Inhibitors on Second Primary Cancer Risk in Patients With Metastatic Lung Cancer Using Real-World Data From the TriNetX Network: Retrospective Cohort Study

JMIR Cancer 2025;11:e64900

DOI: 10.2196/64900

PMID: 41118671

PMCID: 12539796

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