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J Immunother Cancer ; 8(1)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32317292

RESUMO

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Colesterol/administração & dosagem , Melanoma/terapia , Recidiva Local de Neoplasia/epidemiologia , Fosfolipídeos/administração & dosagem , Saponinas/administração & dosagem , Neoplasias Cutâneas/terapia , Adjuvantes Imunológicos/efeitos adversos , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Biópsia , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Colesterol/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos , Intervalo Livre de Doença , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Imunogenicidade da Vacina , Masculino , Melanoma/diagnóstico , Melanoma/imunologia , Melanoma/mortalidade , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Fosfolipídeos/efeitos adversos , Saponinas/efeitos adversos , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade
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