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Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease

Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.

Methods

We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.

Results

EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone.

Conclusions

EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.

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Abbreviations

CS:

Corticosteroid

EGFR:

Epidermal growth factor receptor

DAD:

Diffuse alveolar damage

HRCT:

High-resolution computed tomography

ILD:

Interstitial lung disease

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PFS:

Progression-free survival

PS:

Performance status

PSL:

Prednisolone

TKI:

Tyrosine kinase inhibitor

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Correspondence to Kosuke Kashiwabara.

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The authors have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. A signed informed consent was obtained from all individual participants included in the study (five patients who received EGFR-TKI rechallenge).

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No funding for this work was received.

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Kashiwabara, K., Semba, H., Fujii, S. et al. Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease. Cancer Chemother Pharmacol 79, 705–710 (2017). https://doi.org/10.1007/s00280-017-3261-5

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  • DOI: https://doi.org/10.1007/s00280-017-3261-5

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