Prospective Study of Drug-induced Interstitial Lung Disease in Advanced Breast Cancer Patients Receiving Everolimus Plus Exemestane

Annelieke E. C. A. B. Willemsen, Jolien Tol, Nielka P. van Erp, Marianne A. Jonker, Maaike de Boer, Bob Meek, Paul C. de Jong, Coline van Moorsel, Winald R. Gerritsen, Jan C. Grutters, Carla M. L. van Herpen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background Everolimus-related interstitial lung disease (ILD) (also: pneumonitis) poses a difficulty for physicians, as it is hard to discriminate ILD from other causes of respiratory symptoms and to decide on safe treatment continuation. Objective We investigated the capability of pulmonary function tests (PFT), plasma biomarkers, everolimus pharmacokinetics, and FDG-PET to discriminate between everolimus-related ILD and other causes of respiratory problems and to predict the severity of ILD. Patients and methods Women starting treatment with everolimus plus exemestane for advanced breast cancer were included. At baseline and during the first 3 months, respiratory symptoms, PFT with diffusion capacity of the lungs for carbon monoxide corrected for hemoglobin (DLCOc) and forced vital capacity, serum plasma biomarkers (including SP-D and YKL-40), everolimus trough concentration, and F-18-FDG-PET were prospectively recorded. Results Twenty-seven (out of 29 included) patients were evaluable for analysis. Fifteen patients (56%) developed everolimus-related respiratory signs or symptoms and four patients (15%) needed everolimus discontinuation and received corticosteroids. Change in DLCOc differentiated ILD from alternative diagnoses with 0.91 sensitivity and 0.78 specificity. Decrease in DLCOc (non-significant) was greatest in patients who needed everolimus discontinuation. Serum SP-D and YKL-40 could differentiate ILD from alternative diagnoses with 0.83 and 0.83 sensitivity, and 0.85 and 0.62 specificity, respectively. F-18-FDG-PET abnormalities did not precede clinical symptoms. No relationship between ILD and everolimus trough concentration was found. Conclusions This study shows that everolimus-related ILD occurs frequently. Prospective monitoring of DLCOc in combination with measurement of serum SP-D and YKL-40 appear useful to discriminate ILD from other causes of respiratory symptoms. identifier: NCT01978171.

Original languageEnglish
Pages (from-to)441-451
Number of pages11
JournalTargeted Oncology
Issue number4
Publication statusPublished - Aug 2019


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