دورية أكاديمية
Epacadostat plus pembrolizumab versus placebo plus pembrolizumab as first-line treatment for metastatic non-small cell lung cancer with high levels of programmed death-ligand 1: a randomized, double-blind phase 2 study.
| العنوان: | Epacadostat plus pembrolizumab versus placebo plus pembrolizumab as first-line treatment for metastatic non-small cell lung cancer with high levels of programmed death-ligand 1: a randomized, double-blind phase 2 study. |
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| المؤلفون: | Tokito T; Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan. tokitou_takaaki@kurume-u.ac.jp., Kolesnik O; Zaporizhzhya Regional Clinical Oncology Center, Zaporizhzhya State Medical University, Zaporozhye, Ukraine., Sørensen J; Department of Oncology, Centre for Cancer and Organ Diseases, Rigshospitalet, Copenhagen, Denmark., Artac M; Department of Medical Oncology, Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi, Konya, Turkey., Quintela ML; Department of Medical Oncology, Hospital Álvaro Cunqueiro-Complexo Hospitalario Universitario de Vigo, Vigo, Spain., Lee JS; Division of Hematology-Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea., Hussein M; Florida Cancer Specialists, Tavares, FL, USA., Pless M; Department of Medical Oncology, Kantonsspital Winterthur, Winterthur, Switzerland., Paz-Ares L; Department of Medical Oncology, Hospital Universitario, 12 de Octubre, Universidad Complutense & Ciberonc, Madrid, Spain., Leopold L; Incyte Corporation, Wilmington, DE, United States., Daniel J; Incyte Corporation, Wilmington, DE, United States., Munteanu M; Incyte Corporation, Wilmington, DE, United States., Samkari A; Merck & Co., Inc., Rahway, NJ, United States., Xu L; Merck & Co., Inc., Rahway, NJ, United States., Butts C; Department of Oncology, Division of Medical Oncology, Cross Cancer Institute, Edmonton, Canada. |
| المصدر: | BMC cancer [BMC Cancer] 2024 Jul 25; Vol. 23 (Suppl 1), pp. 1251. Date of Electronic Publication: 2024 Jul 25. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase II; Randomized Controlled Trial; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central, [2001- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/mortality , Antibodies, Monoclonal, Humanized*/administration & dosage , Antibodies, Monoclonal, Humanized*/therapeutic use , Antibodies, Monoclonal, Humanized*/adverse effects , Lung Neoplasms*/drug therapy , Lung Neoplasms*/pathology , Lung Neoplasms*/mortality , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects , B7-H1 Antigen*/antagonists & inhibitors , Sulfonamides*/administration & dosage , Sulfonamides*/therapeutic use , Sulfonamides*/adverse effects, Humans ; Male ; Female ; Middle Aged ; Aged ; Double-Blind Method ; Adult ; Oximes/administration & dosage ; Oximes/therapeutic use ; Oximes/adverse effects ; Aged, 80 and over ; Progression-Free Survival |
| مستخلص: | Background: Pembrolizumab is a first-line therapy for certain patients with advanced/metastatic non-small cell lung cancer (NSCLC). Combining pembrolizumab with other immunotherapies may enhance tumor cell killing and clinical outcomes. Epacadostat is a selective inhibitor of indoleamine 2,3-dioxygenase 1, an immuno-regulatory enzyme involved in tryptophan to kynurenine metabolism that inhibits T cell-mediated immune responses. Methods: In this randomized phase II study, patients with metastatic NSCLC expressing high (≥ 50%) programmed death-ligand 1 (PD-L1) levels received pembrolizumab 200 mg every 21 days plus oral epacadostat 100 mg twice daily (combination) or matching placebo (control). The primary objective was objective response rate (ORR); secondary objectives were progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety/tolerability. Results: 154 patients were randomized (77 per group). Median (range) follow-up was 6.8 months (0.1-11.4) and 7.0 months (0.2-11.9) in the combination and control groups, respectively Confirmed ORR was similar between groups (combination: 32.5%, 95% CI 22.2-44.1; control: 39.0%, 95% CI 28.0-50.8; difference: - 6.5, 95% CI - 21.5 to 8.7; 1-sided P = 0.8000). Median (range) DOR was 6.2 months (1.9 + to 6.5 +) and not reached (1.9 + to 8.6 +) in the combination and control groups, respectively. Although not formally tested, median PFS was 6.7 and 6.2 months for the combination and control groups, respectively, and median OS was not reached in either group. Circulating kynurenine levels increased from C1D1 to C2D1 (P < 0.01) in the control group and decreased from C1D1 to C2D1 (P < 0.01) in the combination group but were not normalized in most patients. The most frequent serious adverse events (AEs) (≥ 2%) were pneumonia (4.0%), anemia (2.7%), atelectasis (2.7%) and pneumonitis (2.7%) in the combination group and pneumonia (3.9%), pneumonitis (2.6%) and hypotension (2.6%) in the control group. Two deaths due to drug-related AEs were reported, both in the control group. Conclusions: Addition of epacadostat to pembrolizumab therapy for PD-L1-high metastatic NSCLC was generally well tolerated but did not demonstrate an improved therapeutic effect. Evaluating higher doses of epacadostat that normalize kynurenine levels when given in combination with checkpoint inhibitors may be warranted. Trial Registration: ClinicalTrials.gov, NCT03322540. Registered 10/26/2017. (© 2023. The Author(s).) |
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| فهرسة مساهمة: | Keywords: Combination immunotherapy; Epacadostat; Non-small cell lung cancer; PD-L1 high; Pembrolizumab |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03322540 |
| المشرفين على المادة: | DPT0O3T46P (pembrolizumab) 0 (Antibodies, Monoclonal, Humanized) 71596A9R13 (epacadostat) 0 (B7-H1 Antigen) 0 (Sulfonamides) 0 (CD274 protein, human) 0 (Oximes) |
| تواريخ الأحداث: | Date Created: 20240725 Date Completed: 20240726 Latest Revision: 20240728 |
| رمز التحديث: | 20240728 |
| مُعرف محوري في PubMed: | PMC11270761 |
| DOI: | 10.1186/s12885-023-11203-8 |
| PMID: | 39054476 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1471-2407 |
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| DOI: | 10.1186/s12885-023-11203-8 |