Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer: A Randomized Clinical Trial

Mené sur 169 patientes atteintes d'un cancer du sein ERBB2- de stade métastatique (âge médian : 58 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'indoximod à une chimiothérapie de première ligne à base de taxane (paclitaxel ou docétaxel)

Résumé en anglais

Importance : Indoleamine 2,3-dioxygenase 1 (IDO1) causes tumor immune suppression. The IDO1 pathway inhibitor indoximod combined with a taxane in patients with ERBB2-negative metastatic breast cancer was tested in a prospective clinical trial.

Objective : To assess clinical outcomes in patients with ERBB2-negative metastatic breast cancer treated with indoximod plus a taxane.

Design, Setting, and Participants :This phase 2 double-blinded randomized 1:1 placebo-controlled clinical trial enrolled patients at multiple international centers from August 26, 2013, to January 25, 2016. Eligibility criteria included ERBB2-negative metastatic breast cancer, ability to receive taxane therapy, good performance status, normal organ function, no previous immunotherapy use, and no autoimmune disease. The study was discontinued in June 2017 because of lack of efficacy. Data analysis was performed from February 2019 to April 2020.

Interventions : A taxane (paclitaxel [80 mg/m2] weekly 3 weeks on, 1 week off, or docetaxel [75 mg/m2] every 3 weeks) plus placebo or indoximod (1200 mg) orally twice daily as first-line treatment.

Main Outcomes and Measures : The primary end point was progression-free survival (PFS); secondary end points were median overall survival, objective response rate, and toxic effects. A sample size of 154 patients would detect a hazard ratio of 0.64 with 1-sided