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  • [Clin Cancer Res. ] 18F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial.

    CNIO-Spanish National Cancer Research Center / Miguel Quintela-Fandino*

  • 출처
    Clin Cancer Res.
  • 등재일
    2017 Mar 15
  • 저널이슈번호
    23(6):1432-1441. doi: 10.1158/1078-0432.CCR-16-0738. Epub 2016 Sep 1.
  • 내용

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    Abstract


    Purpose: We previously detected promising efficacy of neoadjuvant nintedanib (a multityrosine kinase inhibitor, TKI) in early HER2-negative breast cancer. In a preclinical study, we monitored stromal hypoxia with 18F-fluoromisonidazole-positron emission tomography (18F-FMISO-PET); we found that reoxygenation of tumors (or lack of it) during a window-of-opportunity (WoO) treatment with TKIs correlated with the benefit (or lack of it) from TKI-plus-chemotherapy combinations. We studied the predictive role of 18F-FMISO-PET for the TKI nintedanib in the neoadjuvant setting in a phase II WoO randomized trial.

     

    Experimental Design: Patients were randomized to a 14-day WoO of nintedanib preceded and followed by an 18F-FMISO-PET, followed by nintedanib plus weekly paclitaxel (Arm A) or an 18F-FMISO-PET followed by weekly paclitaxel (Arm B) before surgery. The endpoint was residual cancer burden (RCB). The objective was to detect the patients with no response (RCB-III) on the basis of the baseline or evolutive 18F-FMISO-PET values/changes.Results: One-hundred and thirty HER2-negative patients were randomized. Seventeen (27.9%), 34 (55.7%), and 8 (13.1%) patients had an RCB of III, II, and I/0, respectively, in Arm A. In this arm, baseline hypoxic tumors had a 4.4-fold higher chance of experiencing RCB = 3 (P = 0.036) compared with baseline normoxic tumors. Nintedanib WoO induced tumor reoxygenation in 24.5% of the patients; those not reoxygenating showed a trend toward higher chance of experiencing RCB-III (6.4-fold; P = 0.09). In Arm B, 18F-FMISO-PET lacked predictive/prognostic value.

     

    Conclusions: Baseline hypoxic tumors (measured with 18F-FMISO-PET) do not benefit from neoadjuvant nintedanib.  

     

    Author information

    Quintela-Fandino M1, Lluch A2, Manso L3, Calvo I4, Cortes J5,6, García-Saenz JA7, Gil-Gil M8, Martinez-Jánez N6, Gonzalez-Martin A9, Adrover E10, de Andres R11, Viñas G12, Llombart-Cussac A13, Alba E14, Guerra J15, Bermejo B2, Zamora E5, Moreno-Anton F7, Pernas Simon S8, Carrato A6, Lopez-Alonso A16, Escudero MJ17, Campo R17, Carrasco E17, Palacios J18, Mulero F19, Colomer R20.

    Breast Cancer Clinical Research Unit, CNIO - Spanish National Cancer Research Center, Madrid, Spain. mquintela@cnio.es.

    Medical Oncology Department, Hospital Clinico Universitario, Valencia, Spain.

    Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain.

    Medical Oncology Department, Hospital de Montepríncipe, Madrid, Spain.

    Medical Oncology Department, Hospital Vall d'Hebron, Barcelona, Spain.

    Medical Oncology Department, Hospital Ramón y Cajal, Madrid, Spain.

    Medical Oncology Department, Hospital Clinico San Carlos, Madrid, Spain.

    Medical Oncology Department, Institut Catala d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Spain.

    Medical Oncology Department, MD Anderson Cancer Center, Madrid, Spain.

    10 Medical Oncology Department, Hospital General de Albacete, Albacete, Spain.

    11 Medical Oncology Department, Hospital Lozano Blesa, Zaragoza, Spain.

    12 Medical Oncology Department, Institut Catala d'Oncologia-Josep Trueta, Girona, Spain.

    13 Medical Oncology Department, Hospital Arnau de Vilanova, Valencia, Spain.

    14 Medical Oncology Department, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain.

    15 Medical Oncology Department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain.

    16 Breast Cancer Clinical Research Unit, CNIO - Spanish National Cancer Research Center, Madrid, Spain.

    17 GEICAM, Madrid, Spain.

    18 Pathology Department, Hospital Ramon y Cajal, Madrid, Spain.

    19 Molecular Imaging Unit, CNIO - Spanish National Cancer Research Center, Madrid, Spain.

    20 Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain. 

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