Ado-trastuzumab emtansine (T-DM1) induced pulmonary toxicity: A retrospective analysis of a single institution experience.

Abstract

e13004 Background: T-DM1 is an antibody drug conjugate with proven efficacy in metastatic breast cancer for progressive disease refractory to trastuzumab. FDA prescribing information cites a pneumonitis incidence of 0.8% (7/884 cases) based on clinical trial experience. We sought to identify the incidence of this toxicity at our institution. Furthermore, we attempted to identify potential risk factors for drug induced pneumonitis and examine the clinical course leading to resolution of pulmonary symptoms. Methods: We performed a retrospective analysis of EMR data inclusive of all women and men, age 18 and older, treated with T-DM1 at out institution from 1/1/2013-11/1/2017 for breast cancer. Records were reviewed for clinical symptoms and or radiographic evidence concerning for pneumonitis. We identified variables of interest with regard to potential risk factors for toxicity. Results: Upon review, 50 patients were included, 6 (12%) of whom had radiographic and/or clinical symptoms concerning for T-DM1 induced pneumonitis. Grade 3 pneumonitis was observed in 3/6 patients. All 6 patients had metastatic or unresectable breast cancer. Out of the 6 patients, 5 (83%) had suspected pulmonary metastases, 1 (17%) had a history of underlying lung disease, and 5 (83%) had a history of prior taxane therapy. Pulmonary metastases (p=0.38), median number of treatment cycles (p=0.29), prior taxane (p=1), underlying lung disease (p=1), and hormone receptor positivity (p=0.66) did not meet statistical significance for an association with pneumonitis. Time (days) on T-DM1 did not predict for pneumonitis (p=0.32). Steroids were given in 4/6 of the cases, with a time to complete resolution of 29.6 days (range 3-81 days). Conclusions: Pneumonitis is a recognized toxicity of T-DM1. While our sample size is small, the number of events was higher than described in the literature, which may be an artifact of referral bias. Future studies with a larger sample population may detect potential risk factors for toxicity. Reassuringly, patients who received steroids with cessation of T-DM1 achieved improvement of pneumonitis and resolution of symptoms.