University of Oulu

Virve Alanen, Sanna Iivanainen, Martti Arffman, Jussi Pekka Koivunen, Tetracyclines increase the survival of NSCLC patients treated with EGFR TKIs: a retrospective nationwide registry study, ESMO Open, Volume 5, Issue 5, 2020, e000864, ISSN 2059-7029,

Tetracyclines increase the survival of NSCLC patients treated with EGFR TKIs : a retrospective nationwide registry study

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Author: Alanen, Virve1,2; Iivanainen, Sanna1,2; Arffman, Martti3;
Organizations: 1Oncology and Radiotherapy, Pohjois-Pohjanmaan Sairaanhoitopiiri, Oulu, Finland
2MRC Oulu, Oulu University, Oulu, Finland
3National Institute for Health and Welfare, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: BMJ, 2020
Publish Date: 2021-01-29


Background: With the first and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with tetracyclines, but it is unknown whether the use of tetracyclines can increase the survival of non-small-cell lung cancer (NSCLC) patients treated with EGFR TKIs.

Methods: We collected all the patients (n=1271) who had reimbursement for EGFR TKIs (gefitinib, erlotinib and afatinib) in Finland 2011–2016, had purchased TKIs, and had data available at nationwide cancer registry. The survival was analysed from the first EGFR TKI purchase to death or end-of follow-up, and patients were stratified according to TKIs, purchases of antibiotics, their ATC class and timing.

Results: 802 (63.1%) patients had antibiotic purchases −14 to +200 days from the first EGFR TKI purchase, 447 of these tetracyclines. 322 (25.3%) had had purchased antibiotics −14 to +14 days (prophylaxis) from the first EGFR TKI purchase, 188 of these tetracyclines. Purchase of antibiotics was associated with improved survival (HR 0.80, 95% CI 0.71 to 0.91), which limited to tetracycline purchases only (HR 0.72, 95% CI 0.64 to 0.82). The largest survival benefit was seen with the prophylactic use of tetracyclines (HR 0.74, 95% CI 0.62 to 0.88). The benefit from tetracyclines was limited to erlotinib only (HR 0.68, 95% CI 0.58 to 0.78) which was retained in multivariate analysis. Prophylactic use of tetracyclines was associated with a longer erlotinib treatment duration (HR 0.81, 95% CI 0.61 to 0.96) but not with dose reductions or treatment breaks.

Conclusions: Tetracyclines improve the survival of NSCLC patients treated with the first and second-generation EGFR TKIs and they should be considered as a prophylaxis when initiating EGFR TKIs with high incidence of rash.

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Series: ESMO open
ISSN: 2059-7029
ISSN-E: 2059-7029
ISSN-L: 2059-7029
Volume: 5
Issue: 5
Article number: e000864
DOI: 10.1136/esmoopen-2020-000864
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by the University of Oulu, Oulu University Hospital, and Finnish Cancer Institute.
Copyright information: © Author (s) (or their employer(s)) 2020. Re- use permitted under CC BY- NC. No commercial re- use. Published by BMJ on behalf of the European Society for Medical Oncology.