Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors

P E Heudel; A de Montfort; D Debieuvre; C Chouaid; M Carton; C Audigier-Valette; T Filleron; S Chabaud; A Stancu; X Quantin; S Hiret; L Bosquet; J Y Blay

doi:10.1016/j.lungcan.2023.107280

Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors

Lung Cancer. 2023 Aug:182:107280. doi: 10.1016/j.lungcan.2023.107280. Epub 2023 Jun 16.

Authors

P E Heudel¹, A de Montfort², D Debieuvre³, C Chouaid⁴, M Carton⁵, C Audigier-Valette⁶, T Filleron⁷, S Chabaud², A Stancu⁸, X Quantin⁹, S Hiret¹⁰, L Bosquet¹¹, J Y Blay¹²

Affiliations

¹ Centre Léon Bérard, Lyon, France. Electronic address: Pierre-etienne.heudel@lyon.unicancer.fr.
² Biostatistical Unit, Centre Léon Bérard, Lyon, France.
³ Groupe hospitalier de la région de Mulhouse Sud Alsace, Mulhouse, France.
⁴ Centre hospitalier Intercommunal, Créteil, France.
⁵ Biostatistical Unit, Institut Curie, Paris, France.
⁶ Centre hospitalier intercommunal de Toulon - La Seyne-sur-Mer, Toulon, France.
⁷ Biostatistics & Health Data Science Unit, Institut Claudius Régaud IUCT-O, Toulouse, France.
⁸ Institut Sainte Catherine, Avignon, France.
⁹ Institut régional du cancer, Montpellier, France.
¹⁰ Institut de cancérologie de l'Ouest, Angers&Nantes, France.
¹¹ Health Data and Partnership Department, Unicancer, Paris, France.
¹² Centre Léon Bérard, Lyon, France.

PMID: 37339550
DOI: 10.1016/j.lungcan.2023.107280

Abstract

Background: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer.

Patients and methods: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC.

Results: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58).

Conclusion: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

Keywords: Immune check points inhibitors; Immunotherapy; Lung cancer; Second malignant neoplasia; Second primary cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Immune Checkpoint Inhibitors / therapeutic use
Lung
Lung Neoplasms* / drug therapy
Lung Neoplasms* / epidemiology
Neoplasms, Second Primary*
Propensity Score
Retrospective Studies

Substances

Immune Checkpoint Inhibitors