Details

Autor(en) / Beteiligte

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

Titel

18F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial

Ist Teil von

• Clinical cancer research, 2017-03, Vol.23 (6), p.1432-1441

Ort / Verlag

Philadelphia: American Association for Cancer Research Inc

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

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