Neoadjuvant toripalimab plus axitinib for clear cell renal cell carcinoma with inferior vena cava tumor thrombus: NEOTAX, a phase 2 study.
Signal Transduct Target Ther
; 9(1): 264, 2024 Oct 04.
Article
em En
| MEDLINE
| ID: mdl-39362847
ABSTRACT
The potential benefit of neoadjuvant toripalimab plus axitinib in cases with clear cell renal cell carcinoma (ccRCC) and inferior vena cava tumor thrombus (IVC-TT) remains unclear. NEOTAX was a phase 2 study to investigate the efficacy and safety of neoadjuvant toripalimab plus axitinib in patients with ccRCC and IVC-TT (ChiCTR2000030405). The primary endpoint was the down-staging rate of IVC-TT level. Secondary endpoints included change in TT length, response rate, percentage change in surgical approach, surgical morbidity, progression-free survival (PFS), safety, and biomarker analyses. In all, 25 patients received study treatment, 44.0% (11/25) patients had a reduction in thrombus level, and none experienced an increase in Mayo level. The median change in tumor thrombus length was -2.3 cm (range -7.1 to 1.1 cm). Overall, 61.9% (13/21) patients experienced changes in surgical strategy compared with planned surgery, three patients experienced major complications. The median PFS was 25.3 months (95% CI 17.0-NE). The 1-year PFS was 89.1% (95% CI 62.7-97.2). No any of grade 4 or 5 treatment-related adverse event was identified. Biopsy samples of non-responders exhibited increased T cytotoxic cell infiltration, but these cells were predominantly PD-1 positive. Biopsy samples of responders exhibited lower T helper cells, however, their subtype, regulatory T cells remained unchanged. In surgical samples of the TT, non-responders exhibited increased CD8T_01_GZMK_CXCR4 subset T cells. NEOTAX met preset endpoints proving that toripalimab in combination with axitinib downstages IVC-TT in a significant proportion of patients leading to simplification in the procedure of surgery.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Veia Cava Inferior
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Carcinoma de Células Renais
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Protocolos de Quimioterapia Combinada Antineoplásica
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Terapia Neoadjuvante
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Anticorpos Monoclonais Humanizados
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Axitinibe
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Neoplasias Renais
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article