American Association for Cancer Research
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Supplementary figure legends from 18F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial

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posted on 2023-03-31, 19:30 authored by Miguel Quintela-Fandino, Ana Lluch, Luis Manso, Isabel Calvo, Javier Cortes, José Angel García-Saenz, Miguel Gil-Gil, Noelia Martinez-Jánez, Antonio Gonzalez-Martin, Encarna Adrover, Raquel de Andres, Gemma Viñas, Antonio Llombart-Cussac, Emilio Alba, Juan Guerra, Begoña Bermejo, Esther Zamora, Fernando Moreno-Anton, Sonia Pernas Simon, Alfredo Carrato, Antonio Lopez-Alonso, María José Escudero, Ruth Campo, Eva Carrasco, José Palacios, Francisca Mulero, Ramon Colomer

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AECC Scientific Foundation 2010

AVON Spain Inc.

Boehringer-Ingelheim Spain



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. Clin Cancer Res; 23(6); 1432–41. ©2016 AACR.