Long Term Effects of EGFR Tyrosine Kinase Inhibitor Therapy on the Non-Neoplastic Lung
Namrata Setia, Pasi A Janne, Lynette M Sholl. Brigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA
Background: Erlotinib, an EGFR tyrosine kinase inhibitor (TKI) was FDA-approved for treatment of advanced non small cell lung carcinoma (NSCLC) in 2004. Side effects of EGFR TKIs include interstitial pneumonitis, typically early in the course of therapy. Little is known, however, about the long term effects of EGFR TKI therapy. In this study, we examine the histology of non-neoplastic lung in patients receiving long-term EGFR TKI therapy for advanced NSCLC.
Design: Long term EGFR TKI therapy was defined as approximately 1 year or more. Cases were selected from the pathology department autopsy files based on a diagnosis of NSCLC, a history of treatment with erlotinib or other TKI therapy, and availability of lung tissue for histologic evaluation. Additional surgical specimens were identified from the authors' files. Demographic and clinical features, including history of lung disease, occupational exposures, smoking history, tumor EGFR mutation status, and treatment history was extracted from the medical record. Slides were reviewed for pathologic changes in the nonneoplastic lung in areas free of tumor and/or acute peri-mortem changes, for the autopsy cases.
Results: Seven cases (5 autopsies and 2 pulmonary wedge resections) were included. Patients received erlotinib for a mean of 38.3 (range 11-88) months. Mean age at diagnosis was 64.2 (range 47-79) years; 5 were male and 2 were female. None of the patients had a prior history of pulmonary fibrosis or significant occupational exposures. One patient was a smoker. All tumors contained an EGFR activating mutation. Prior to erlotinib therapy, all patients received ≥2 chemotherapeutic drugs, three patients received radiation therapy, and one had a lobectomy for tumor removal. The following histologic findings were noted: patchy mild-moderate interstitial fibrosis (3/7), fibroblastic foci (1/7), focal organizing pneumonia (2/7), obliterative bronchiolitis (2/7), hypersensitivity pneumonitis (1/7), pulmonary hypertensive changes (5/7) and organizing thrombi (2/7).
Conclusions: Relatively minor changes were seen in the non-neoplastic lungs of patients undergoing long term erlotinib therapy. However, obliterative bronchiolitis was noted in two cases, raising the possibility that EGFR TKIs may lead to small airways injury in a subset of patients receiving prolonged therapy. With advancements in targeted cancer therapies and associated improvements in patient survival time, the pulmonary effects of chronic EGFR TKI therapy may become clinically significant.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 295, Tuesday Afternoon