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1.
Cancer ; 126(16): 3689-3697, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32525561

RESUMEN

BACKGROUND: Antiangiogenic-targeting agents have low response rates in patients with nonpancreatic neuroendocrine tumors (NETs). Nintedanib is an oral antiangiogenic agent that has inhibitory effects on the fibroblast growth factor receptor, which is highly expressed in NETs. The authors hypothesized that nintedanib would be active in patients with nonpancreatic NETs. METHODS: Patients with advanced, grade 1 or 2, nonpancreatic NETs who were receiving a stable dose of somatostatin analogue were enrolled. Nintedanib was administered at a dose of 200 mg twice daily in 28-day cycles. The primary endpoint was progression-free survival (PFS) at 16 weeks. RESULTS: Thirty-two patients were enrolled, and 30 were evaluable for the primary outcome. Most had radiographic disease progression within 12 months before enrollment. The 16-week PFS rate was 83%, and the median PFS and overall survival were 11.0 months and 32.7 months, respectively. Nintedanib was well tolerated and delayed deterioration in quality of life. The baseline serotonin level had a strong, positive correlation with activated but exhausted T cells. CONCLUSIONS: Nintedanib is active in nonpancreatic NETs. The immunosuppressive effect of serotonin should be targeted in future clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Indoles/administración & dosificación , Neovascularización Patológica/tratamiento farmacológico , Tumores Neuroendocrinos/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/patología , Supervivencia sin Progresión , Somatostatina/administración & dosificación , Somatostatina/efectos adversos , Resultado del Tratamiento
2.
Clin Cancer Res ; 29(4): 731-741, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36255391

RESUMEN

PURPOSE: Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in peripheral blood. PATIENTS AND METHODS: NCT03728361 is a nonrandomized, phase II study of nivolumab and temozolomide in patients with NEN. The primary endpoint was response rate using RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Immune profiling was performed by mass cytometry to evaluate the effect on peripheral blood immune cell subsets. RESULTS: Among all 28 patients with NEN, the confirmed response rate was 9/28 [32.1%, 95% confidence interval (CI): 15.9-52.4]. Of 11 patients with lung NEN, the response rate was 64% (n = 7); there was a significant difference in responses by primary tumor location (lung vs. others, P = 0.020). The median PFS was 8.8 months (95% CI: 3.9-11.1 months), and median OS was 32.3 months (95% CI: 20.7-not reached months). Exploratory blood immune cell profiling revealed an increase in circulating CD8+ T cells (27.9% ± 13.4% vs. 31.7% ± 14.6%, P = 0.03) and a decrease in CD4+ T cells (59.6% ± 13.1% vs. 56.5% ± 13.0%, P = 0.001) after 2 weeks of treatment. LAG-3-expressing total T cells were lower in patients experiencing a partial response (0.18% ± 0.24% vs. 0.83% ± 0.55%, P = 0.028). Myeloid-derived suppressor cell levels increased during the study and did not correlate with response. CONCLUSIONS: Combination nivolumab and temozolomide demonstrated promising activity in NEN. See related commentary by Velez and Garon, p. 691.


Asunto(s)
Neoplasias Pulmonares , Tumores Neuroendocrinos , Humanos , Nivolumab/uso terapéutico , Temozolomida/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Tumores Neuroendocrinos/tratamiento farmacológico , Supervivencia sin Progresión
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