Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 14;23(1):247.
doi: 10.1186/s12885-023-10701-z.

A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer

Hanieh Abedian Kalkhoran  1   2 , Juliëtte Zwaveling  3 , Bert N Storm  4 , Sylvia A van Laar  3 , Johanneke Ea Portielje  5 , Henk Codrington  6 , Dieuwke Luijten  6 , Pepijn Brocken  6 , Egbert F Smit  7 , Loes E Visser  4   8   9
Affiliations

A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer

Hanieh Abedian Kalkhoran et al. BMC Cancer. .

Abstract

Background: This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique.

Methods: This retrospective study included patients with stage III/IV NSCLC treated with a PD-(L)1 inhibitor (nivolumab, pembrolizumab, atezolizumab and durvalumab) at Leiden University Medical Centre and Haga Teaching hospital, (both in The Netherlands) from September 2016 to May 2021. All the relevant data was extracted from the structured and unstructured fields of the Electronic Health Records using a novel text-mining tool. Effectiveness [progression-free survival (PFS) and overall survival (OS)] and safety (the incidence of nine potentially fatal irAEs and systemic corticosteroid requirement) outcomes were compared across age subgroups (young: < 65 years, Middle-aged: 65-74 years, and old: ≥ 75 years) after adjustment for confounding.

Results: Of 689 patients, 310 patients (45.0%) were < 65 years, 275 patients (39.9%) were aged between 65 and 74 years, and 104 patients (15.1%) were ≥ 75 years. There was no significant difference between younger and older patients regarding PFS (median PFS 12, 8, 13 months respectively; Hazard ratio (HR)middle-aged = 1.14, 95% CI 0.92-1.41; HRold = 1.10, 95% CI 0.78-1.42). This was also the case for OS (median OS 19, 14, 18 months respectively; HRmiddle-aged = 1.22, 95% CI 0.96-1.53; HRold = 1.10, 95% CI 0.79-1.52). Safety analysis demonstrated a higher incidence of pneumonitis among patients aged 65-74. When all the investigated irAEs were pooled, there was no statistically significant difference found between age and the incidence of potentially fatal irAEs.

Conclusions: The use of PD-(L)1 inhibitors is not associated with age related decrease of PFS and OS, nor with increased incidence of serious irAEs compared to younger patients receiving these treatments. Chronological age must therefore not be used as a predictor for the effectiveness or safety of ICIs.

Keywords: Anti-PD-(L)1 therapy; Elderly; Immune checkpoint inhibitor (ICI); Non-small cell lung cancer (NSCLC); Real-world.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Study selection process
Fig. 2
Fig. 2
Kaplan–Meier survival plots according to age groups. (A) Progression free-survival, (B) overall survival. CI, confidence interval
Fig. 3
Fig. 3
Multivariable Cox regression analysis: PFS and OS of patients aged 65–74 and > 75 years compared with younger patients (< 65 years). CI = confidence interval *HR adjusted for BMI, smoking status and ECOG PS
Fig. 4
Fig. 4
The safety outcomes between different age groups A the overall incidence of each of the nine studied potentially fatal irAEs (nr. of patients), B the percentage of patients experiencing one of the studied irAE per age subgroup and in total (%), C relative risk of pooled potentially fatal irAEs (reference: patients aged < 65 years), D relative risk of systemic corticosteroid therapy requirement during (+ 6 months after) immunotherapy (reference: patients aged < 65 years
See this image and copyright information in PMC

References

    1. World Health Organization. 2021. Fact sheet cancer. [online] Available at: <https://www.who.int/news-room/fact-sheets/detail/cancer> [Accessed 20 June 2021].
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590. - DOI - PubMed
    1. Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94(8):1623–1640. doi: 10.1016/j.mayocp.2019.01.013. - DOI - PubMed
    1. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–135. doi: 10.1056/NEJMoa1504627. - DOI - PMC - PubMed
    1. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–1639. doi: 10.1056/NEJMoa1507643. - DOI - PMC - PubMed

MeSH terms

Substances