Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
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 α = .1 and β = .2 after 95 events. Archival tumor tissue was stained with immunohistochemistry for IDO1 expression as an exploratory analysis. RESULTS: Of 209 patients enrolled, 169 were randomized and 164 were treated (85 in the indoximod arm; 79 in the placebo arm). The median (range) age was 58 (29-85) years; 166 (98.2%) were female, and 135 (79.9%) were White. The objective response rate was 40% and 37%, respectively (indoximod vs placebo) (P = .74). The median (range) follow-up time was 17.4 (0.1-39.4) months. The median PFS was 6.8 months (95% CI, 4.8-8.9) in the indoximod arm and 9.5 months (95% CI, 7.8-11.2) in the placebo arm (hazard ratio, 1.2; 95% CI, 0.8-1.8). Differences between the experimental and placebo arms in median PFS (6.8 vs 9.5 months) and overall survival (19.5 vs 20.6 months) were not statistically significant. Grade 3 or greater treatment-emergent adverse events occurred in 60% of patients in both arms. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that, among patients with ERBB2-negative metastatic breast cancer, addition of indoximod to a taxane did not improve PFS compared with a taxane alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01792050.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer
- Date Crossref
- 01/01/2021
- Éditeur
- American Medical Association (AMA)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Moffitt Cancer Center pays non établi dans la noticeÉtablissement de santé
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University of Mississippi pays non établi dans la noticeUniversité ou école supérieure
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University of Virginia pays non établi dans la noticeUniversité ou école supérieure
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Cleveland Clinic pays non établi dans la noticeÉtablissement de santé
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Virginia Commonwealth University pays non établi dans la noticeUniversité ou école supérieure
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Wake Forest University pays non établi dans la noticeUniversité ou école supérieure
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The University of Texas MD Anderson Cancer Center pays non établi dans la noticeÉtablissement de santé
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NewLink Genetics (United States) pays non établi dans la noticeEntreprise
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University of Illinois Chicago pays non établi dans la noticeUniversité ou école supérieure
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Lankenau Institute for Medical Research pays non établi dans la noticeOrganisation à but non lucratif
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NewLink Genetics Corporation pays non établi dans la noticeInstitution
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University of Illinois at Chicago pays non établi dans la noticeUniversité ou école supérieure
Moffitt Cancer Center, University of Mississippi et University of Virginia, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.