Use of [18F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [18F]-FDG PET-predicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial

Coudert, B.; Pierga, Jean‐Yves; Mouret-Reynier, Marie-Ange; Kerrou, K.; Ferrero, Jean-­Marc; Petit, Thierry; Kerbrat, Pierre; Dupré, Pierre‐François; Bachelot, Thomas; Gabelle, Philippe; Giard, S.; Coeffic, D.; Bougnoux, Philippe; Prevost, Jean-Briac; Paintaud, Gilles; Thibault, Gilles; Hernandez, Juana; Coudert, Mathieu; Arnould́, Laurent; Berriolo‐Riedinger, Alina

doi:10.1016/s1470-2045(14)70475-9

Cited by 119 publications

(86 citation statements)

References 28 publications

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“…Nevertheless, it is still not clear whether an increased pCR rate, due to a novel treatment, translates into improved survival (12). This is a crucial issue for the design of future PET-guided therapeutic trials to evaluate the benefit of an early therapeutic switch in nonresponding women (45).…”

Section: Limitations Of the Studymentioning

confidence: 99%

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Humbert

Riedinger

Charon-Barra

et al. 2015

Clinical Cancer Research

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Purpose: To investigate the value of the metabolic tumor response assessed with 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC).Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (DSUV max ) were assessed using FDG-PET.Results: The pCR rate was 42%. High Ki-67 proliferation index (P ¼ 0.016), negative EGFR status (P ¼ 0.042), and high DSUV max (P ¼ 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P ¼ 0.043) and high DSUV max (OR, 7.1; P ¼ 0.014) were independent predictors of pCR. Using a threshold at À50%, tumor DSUV max predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low DSUV max and positive EGFR status could predict non-pCR with an accuracy of 92%.Conclusions: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials.

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Section: Limitations Of the Studymentioning

confidence: 99%

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Humbert

Riedinger

Charon-Barra

et al. 2015

Clinical Cancer Research

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“…However, in the study conducted by our group (51), the hormone receptor status of the tumor was the most powerful predictor of a pCR. Furthermore, (50). The authors demonstrated that the pCR rate was higher when bevacizumab was added than when the neoadjuvant therapy was unchanged.…”

Section: Clinical Settingmentioning

confidence: 98%

“…The other studies scheduled early 18 F-FDG PET/CT up front after 1 or 2 cycles of a taxaneand trastuzumab-based combination (48)(49)(50).…”

Section: Clinical Settingmentioning

confidence: 99%

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Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

et al. 2016

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Since the approval of trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER2), 3 other HER2-targeting agents have gained regulatory approval: lapatinib, pertuzumab, and trastuzumab-emtansine. These agents have revolutionized the management of HER2-positive breast cancer, highlighting the concept that targeted therapies are successful when patients exhibit tumor-selective expression of a molecular target-in this case, HER2. However, response prediction and innate or acquired resistance remain serious concerns. Predictive biomarkers of a response-which could help in the selection of patients who might benefit from a selected targeted therapy-are currently lacking. Molecular imaging with anti-HER2 probes allows the noninvasive, whole-body assessment of HER2 tumor burden and has the potential to improve patient selection, optimize the dose and schedule, and rationalize assessment of the response to anti-HER2 therapies. Furthermore, unlike biopsy-based HER2 assessment, this approach can reveal inter-or intratumoral heterogeneity as well as variations in HER2 expression over time. This review summarizes the available literature and the current status of molecular imaging as a tool for the assessment of HER2 (target) expression or the prediction of an early treatment response in early and advanced HER2-positive breast cancer. Human epidermal growth factor receptor 2 (HER2) is overexpressed in several cancers, including breast, gastric, ovary, prostate, bladder, and lung cancers, and is a proven therapeutic target in the first 2 tumor types (1,2). In breast cancer (BC), in particular, HER2 overexpression is found in 15%-25% of patients and is associated with a clinically aggressive course. Successful targeting of HER2 with a range of anti-HER2 drugs has resulted in markedly improved patient outcomes in both advanced and early disease settings (3).However, the presence of a target (in this case, HER2) does not always guarantee benefit from matched targeted therapies because downstream signaling resistance or escape can occur. In HER2-overexpressing BC, it has been estimated that about 50% of patients with metastases do not benefit from anti-HER2 therapies (4), and not a single biomarker for identifying nonresponding patients has yet been validated (5).Furthermore, there is increasing evidence of temporal and spatial heterogeneity in BC HER2 overexpression. Patients with negative test results at diagnosis can have positive test results later in the disease course and vice versa, a fact that explains why biopsy of metastatic disease is a strong recommendation of many clinical treatment guidelines (6). Heterogeneity in biomarker expression at metastatic sites is only beginning to be recognized, with growing appreciation for molecular imaging.This article focuses on HER2-positive BC and provides a comprehensive overview of the present and future roles of molecular imaging in improving target mapping, predicting benefit from chemotherapy with or without ...

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“…Coudert et al [43] planned the AVATAXHER multicentric phase 2 randomized trial to assess the benefit of adding bevacizumab after the second cycle of treatment in women who responding poorly (DSUV ,70%) to trastuzumab/ docetaxel.The addition of bevacizumab for women with a poor metabolic response increased the pCR rate from 24% to 43.8%. This is the first study suggesting that tailoring the NAC regimen to the early metabolic response might be of clinical benefit.The prognostic value of the metabolic response in this subtype has not been evaluated yet.…”

Section: Her2-positive Subtypementioning

confidence: 99%

Role of Positron Emission Tomography for the Monitoring of Response to Therapy in Breast Cancer

et al. 2015

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This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with 18 F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype.The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor. The Oncologist 2015;20:94-104 Implications for Practice:18 F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a molecular imaging exam. It can monitor breast cancer response to therapy earlier than the tumor shrinking observed with conventional imaging. This review focuses on the advantages and limits of FDG-PET for early determination of response, both in the neoadjuvant and metastatic settings. It discusses the different PET timing and metabolic criteria to define response that have been evaluated in previous studies. The development of new radiotracers of specific molecular pathways of breast cancer cells is also a challenging and promising research area to monitor the effectiveness of the new target treatments emerging in breast cancer.

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Use of [18F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [18F]-FDG PET-predicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial

Cited by 119 publications

References 28 publications

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

Role of Positron Emission Tomography for the Monitoring of Response to Therapy in Breast Cancer

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