التفاصيل البيبلوغرافية
| العنوان: |
Molecular Biomarkers of Prognosis in Advanced Renal Cell Carcinoma Patients Treated With Pazopanib Plus Interferon Alpha (INF-2A) in a Phase I/II Study by the Spanish Oncology Genitourinary Group. |
| المؤلفون: |
García-del-Muro, Xavier, Durán, Ignacio, Perez-Gracia, Jose Luis, Climent, Miguel Ángel, Mellado, Begoña, Virizuela, Juan A., Castellano, Daniel E., González del Alba, Aranzazu, García Carbonero, Iciar, Álvarez-Fernández, Carlos, García-Donas, Jesús, Gil-Martin, Marta, Hernández, Alvaro-González |
| المصدر: |
Clinical Genitourinary Cancer; Aug2022, Vol. 20 Issue 4, p388.e1-388.e10, 10p |
| مصطلحات موضوعية: |
BIOMARKERS, RENAL cell carcinoma, INTERFERON alpha, TREATMENT effectiveness, CANCER immunotherapy |
| مستخلص: |
Phase I/II translational trial evaluating the molecular determinants of pazopanib plus interferon alpha efficacy in advanced renal cell carcinoma. The expression levels of TNF- a, endoglin and PDL1 correlated with response at eight weeks after treatment initiation. This suggests a crucial role of vascular remodelling and inflammatory-mediated immune cell infiltration for an optimal response to pazopanib plus interferon alpha combination. Introduction: The therapeutic repertoire available for advanced renal cell carcinoma (RCC), including tyrosine kinase inhibitors (TKIs) and immunotherapy, required for molecular biomarkers for response. Patients and Methods: This was a phase I to II trial on the combination of pazopanib with interferonalpha (INF-2A) as first-line treatment for advanced RCC. The primary endpoint was recommended phase II dose (RP2D) and efficacy in terms of objective response rate (ORR, RECIST 1.1 criteria). Secondary endpoints included safety and a translational study of molecular biomarkers in serum and exosomes from peripheral blood samples at three-time points: baseline, 8 weeks of treatment, and progression of the disease. Results: Between July 2011 and July 2017, 53 eligible patients were treated and followed up (I, n = 20; II, n = 33). Pazopanib 800 mg + INF-2A 3 MIUs showed a manageable safety profile; therefore, it was selected for dose expansion. Overall, grade 3/4 toxicities were reported in 24 (72.7%) patients. The ORR was 27.2%. The 12-month OS rate was 83.6% (median not reached), and after 30.9 months of followup, 24 (72.7%) patients were still alive. CCL2, IL8, TNF- a, and PD-L1 were significantly overexpressed after treatment initiation, while TGF- ß1 and CCL5 were significantly decreased. TNF- a, endoglin, and PDL1 expression are correlated with the response after treatment initiation. Conclusion: The trial did not reach its pre-specified target ORR. However, OS was longer than expected with pazopanib monotherapy. Changes in the molecular profile suggest a crucial role of vascular remodeling and inflammatory-mediated immune cell infiltration in optimal response to pazopanib plus INF-2A. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
