Antibiotic Treatment is an Independent Poor Risk Factor in NSCLC But Not in Melanoma Patients Who had Received Anti-PD-1/L1 Monotherapy

Hannes Vihinen; Artturi Jokinen; Teemu D Laajala; Nesna Wahid; Lotta Peltola; Tiia Kettunen; Aino Rönkä; Leena Tiainen; Tanja Skyttä; Laura Kohtamäki; Sanni Tulokas; Hanna Karhapää; Micaela Hernberg; Maria Silvoniemi; Kalle E Mattila

doi:10.1016/j.cllc.2023.01.004

Antibiotic Treatment is an Independent Poor Risk Factor in NSCLC But Not in Melanoma Patients Who had Received Anti-PD-1/L1 Monotherapy

Clin Lung Cancer. 2023 Jun;24(4):295-304. doi: 10.1016/j.cllc.2023.01.004. Epub 2023 Jan 24.

Authors

Affiliations

¹ Department of Oncology and Radiotherapy and Fican West Cancer Centre, University of Turku and Turku University Hospital, POB 52, FIN-20521 Turku, Finland.
² Department of Mathematics and Statistics, University of Turku, Turku, Finland.
³ Department of Oncology and Radiotherapy Vaasa Central Hospital, Vaasa Finland.
⁴ Center of Oncology, Kuopio University Hospital, Kuopio, Finland.
⁵ Department of Oncology, Tays Cancer Centre, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶ Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁷ Department of Respiratory Medicine, Turku University Hospital and University of Turku, Turku, Finland.
⁸ Department of Oncology and Radiotherapy and Fican West Cancer Centre, University of Turku and Turku University Hospital, POB 52, FIN-20521 Turku, Finland; InFLAMES Research Flagship Center, University of Turku. Electronic address: kalle.mattila@tyks.fi.

PMID: 36774235
DOI: 10.1016/j.cllc.2023.01.004

Abstract

Background: Antibiotic treatment may reduce the efficacy of cancer immunotherapy by disrupting gut microbiome. We aimed to study the association of antibiotics and survival outcomes in advanced cutaneous melanoma and non-small-cell lung cancer (NSCLC) patients who had received anti-PD-1/L1 monotherapy.

Patients and methods: A total of 222 melanoma and 199 NSCLC patients had received anti-PD-1/L1 monotherapy in 5 Finnish hospitals between January 2014 and December 2020. Clinical characteristics, antibiotic and corticosteroid treatment, and survival outcomes were retrospectively collected from hospital and national medical records.

Results: There were 32% of melanoma and 31% of NSCLC patients who had received antibiotic treatment (ABT) 3 months before to 1 month after the first anti-PD-1/L1 antibody infusion. In survival analyses, early antibiotic treatment was associated with inferior overall survival (OS) (ABT 19.2 [17.6-43.7] vs. no ABT 35.6 [29.3-NA] months, P = .033) but not with inferior progression-free survival (PFS) (ABT 5.8 [3.0-12.6] vs. no ABT 10.2 [7.7-15.3] months, P = .3) in melanoma patients and with inferior OS (ABT 8.6 [6.4-12.3] vs. no ABT 18.5 [15.1-21.6] months, P < .001) and PFS (ABT 2.8 [2.1-4.5] vs. no ABT 5.6 [4.4-8.0] months, P = .0081) in NSCLC patients. In multivariable analyses, ABT was not an independent risk-factor for inferior OS and PFS in melanoma but was associated with inferior OS (hazard ratio [HR] 2.12 [1.37-3.28]) and PFS (HR 1.65 [1.10-2.47]) in NSCLC after adjusted for other risk factors.

Conclusions: Early ABT was an independent poor risk factor in NSCLC patients who had received anti-PD-1/L1 monotherapy but not in melanoma patients. The weight of ABT as a poor risk factor might depend on other prognostic factors in different cancers.

Keywords: Antibiotics; Immune checkpoint inhibitors; Overall survival; Prognostic factor; Progression-free survival.

MeSH terms

Anti-Bacterial Agents / therapeutic use
B7-H1 Antigen
Carcinoma, Non-Small-Cell Lung*
Humans
Lung Neoplasms*
Melanoma* / drug therapy
Retrospective Studies
Skin Neoplasms* / drug therapy

Substances

Anti-Bacterial Agents
B7-H1 Antigen