• Camille Poisson, Alex Hlavaty, Nicolas Favrolt, Marie-Camille Chaumais, Julien Grynblat, Etienne-Marie Jutant, Benoît Lechartier, Arnaud Maurac, Pierre Mouillot, Sylvain Palat, Laurie Rambach, Fabrice Antigny, Vincent Cottin, Guillaume Beltramo, Marc Humbert, KhouriCharlesCUniv. Grenoble-Alpes, Pharmacovigilance Unit, Grenoble-Alpes University Hospital, Grenoble, France; Univ. Grenoble-Alpes, Inserm CIC1406, CHU de Grenoble, Grenoble, France; Univ. Grenoble-Alpes, HP2 Laboratory, Inserm U1300, Grenoble, France, Philippe Bonniaud, and David Montani.
• Service de Pneumologie et Soins Intensifs Respiratoire, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adultes de Dijon, réseau OrphaLung, Filière RespiFil, Centre Hospitalier Universitaire de Bourgogne, Dijon, France; INSERM U1231, Equipe HSP-pathies, Faculty of Medicine and Pharmacy, University of Bourgogne-Franche Comté, Dijon, France.
• Chest. 2024 Nov 19.

BackgroundTrastuzumab emtansine has been recently suspected to be associated with the development of pulmonary arterial hypertension (PAH).Research QuestionIs there an association between trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan and the development of PAH?.Study Design And MethodsCharacteristics of incident PAH cases treated with trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan were analyzed from the French PH Registry, the VIGIAPATH program, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization pharmacovigilance database using a broad definition of pulmonary hypertension (PH) and a narrow definition of PAH. A signal of disproportionate reporting was deemed significant if the lower boundary of the 95% credibility interval of the information component (IC) was superior to 0. The variables were expressed as median (interquartile range).ResultsIn the French PH Registry, we identified 8 incident cases of PAH after trastuzumab emtansine exposure and none with trastuzumab alone or trastuzumab deruxtecan. All cases occurred in females (age, 56; 49-61 years) with breast cancer. The delay between first exposure and PAH diagnosis was 43 months (4.5-55). At diagnosis, 5 were in New York Heart Association functional class III/IV with severe hemodynamic impairment (mean pulmonary artery pressure, 42 mm Hg; cardiac index, 2.51 L/min/m2; pulmonary vascular resistance, 9.7 Wood units). Disproportionality analysis showed that only trastuzumab emtansine demonstrated a significant signal of disproportionate reporting using both a broad definition of PH (IC, 1.46; 0.86-1.95) and a narrow definition of PAH (IC, 1.76; 0.83-2.46). Trastuzumab displayed a significant signal using only the broad definition of PH, whereas trastuzumab deruxtecan was not associated with any significant signals of disproportionate reporting.InterpretationOur results suggest that more patients exposed to trastuzumab emtansine developed PH compared with trastuzumab alone. Further assessment of this safety signal and exploration of pathophysiological mechanisms is needed.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

6 keywords...

hide…