Audrey Bellesoeur's research while affiliated with Institut Curie and other places
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Publications (62)
Background:
The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been eval...
BACKGROUND: The use of two anti-HER2 monoclonal antibodies (mAbs) (pertuzumab and trastuzumab) combined with taxanes is the standard of care for first line treatment in HER2-positive metastatic breast cancer (mBC). Infusion related reactions (IRR) during first administration of anti-HER2 mAb have been reported. Reintroduction of the causal drugs is...
Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). However, the clinical benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has...
Résumé
Les inhibiteurs de PARP (iPARP) ont déjà montré leur efficacité dans différents types tumoraux comme le cancer de l’ovaire, du sein, de la prostate et du pancréas. De nombreuses études sont encore en cours pour élargir leur spectre de prescription. La prescription des inhibiteurs de PARP est quasi exclusivement réservée aux patients présenta...
Background
The risk of drug–drug interactions (DDI) has become a major issue in cancer patients. However, data in sarcoma patients are scarce. We aimed to evaluate the frequency and the factors associated with DDI with antitumor treatments, and to evaluate the impact of a pharmacist evaluation before anticancer treatment.Patients and methodsWe perf...
Breast cancer and gynecological cancers affect more than 3 million women worldwide each year. With advances in precision medicine, a growing number of targeted therapies have been approved recently, and new therapeutic classes have emerged: cell cycle inhibitors for hormone receptor positive breast cancer, antibody drug conjugate for Human Epiderma...
TPS5604
Background: Gynecological carcinosarcomas (CS) are rare and highly aggressive tumors with a 5-year overall survival (OS) < 10%. After initial treatment majority of patients (pts) relapse and receive diverse chemotherapies (CT) producing modest benefits. The median PFS in relapse after platinum based CT is less than 4 months and median OS le...
Background
Palbociclib, a highly selective inhibitor of CDK4/6, is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with an aromatase inhibitor or with fulvestrant for patients who have progressed with an aromatase inhibitor, and in premenopausal women with a luteinis...
Background: The risk of drug drug interactions (DDI) has become a major issue in cancer patient care. However, data in sarcoma patients are scarce. We aimed to evaluate the frequency of DDI with antitumor treatments, identify the risk factors for DDI and evaluate the impact of a pharmacist evaluation before anticancer treatment.
Patients and Method...
Background:
Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience.
Patients and m...
Background
Concerns have emerged about the higher risk of fatal COVID-19 in cancer patients. In this paper, we review the experience of a comprehensive cancer center.
Methods
A prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and actively...
Background: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France).
Cancer treatment has known a revolution with the emergence of immune checkpoint inhibitors. However, accurate theranostic biomarkers are lacking. In this review, we discuss different types of biomarkers currently under investigation. First, we focus on tissue biomarkers including PD-L1 expression by immunohistochemistry—the first Food and Drug Admi...
Background:
Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France).
Methods:
An IRB-approved prospective registry was set up at ICH on March 13,...
Background: Concerns have emerged about the higher risk of fatal COVID-19 in cancer patients. In this paper, we review the experience of a comprehensive cancer center.
Methods: A prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and activel...
Background: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France).
Methods: An IRB-approved prospective registry was set up at ICH for all breast c...
BACKGROUND: Although no survival benefit has been demonstrated by treating early breast cancer (BC) with neoadjuvant chemotherapy (NAC), it is now widely accepted as first intention strategy in triple negative and -positive BC. However, the benefit of the neoadjuvant strategy is controversial in luminal tumours. The latter are considered as poor re...
INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly being used for locally advanced breast cancers (BCs) or aggressive BC tumors. However, no survival benefit of the neoadjuvant approach over receiving chemotherapy in the adjuvant setting has been proven so far in -positive early breast cancer (BC) patients. The objective of this study was...
Background:
The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological paramet...
Background:
The 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care.
Methods:
The CERTIM cohort is a prospe...
Context Anti-PD1 therapy nivolumab has been approved for the treatment of advanced non-small cell lung cancer (NSCLC). However, a large inter-individual variability in its efficacy has been observed. Thus, the search for reliable factors to predict anti-PD1 efficacy represents a major challenge, particularly in NSCLC patients. The aim of this prosp...
Context Anti-PD1 therapy nivolumab has been approved for the treatment of advanced non-small cell lung cancer (NSCLC). However, a large inter-individual variability in its efficacy has been observed. Thus, the search for reliable factors to predict anti-PD1 efficacy represents a major challenge, particularly in NSCLC patients. The aim of this prosp...
e22506
Background: Neoadjuvant chemotherapy with intercalated surgery is the standard of care for resectable high-grade bone sarcoma (BS) but identification of biomarkers for chemosensitivity prediction is still needed. Methods: We recruited 121 pts with new primary localized or metastatic BS, measured fasting blood glucose and insulin, body mass i...
Aims:
Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this...
Résumé
Les thérapies ciblées orales sont une classe de médicaments anti-tumoraux en pleine expansion. À l’issue d’essais cliniques menés sur des populations sélectionnées, ces molécules sont approuvées le plus souvent selon une posologie unique. Pourtant, elles présentent une grande variabilité pharmacocinétique inter et intra-individuelle, et un i...
Dabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that is approved, as monotherapy or in combination with trametinib (mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastatic BRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid cancer harbouring the BRAFV600E mut...
The use of anticoagulants in patients with cancer is challenging as several co-morbidities modifying pharmacokinetic (PK) parameters and significant drug-drug interactions with concomitant anti-neoplastic therapies may lead to PK variability resulting in increased risk of thrombosis or bleeding.
Data on the management of patients with cancer-associ...
Purpose of the study : The 18-gene Tumor Inflammation Signature (TIS) (Ayers et al, J Clin Invest 2017; 127:2930) is a clinical research assay that enriches for clinical response to immune checkpoint blockade. In this work, the performance of the TIS was evaluated on standard tumor specimens for its ability to predict clinical benefit of immunother...
We report the case of a patient with a BRCA2 germline mutation who developed a localized pleomorphic soft tissue sarcoma of the leg with poor prognostic features. BRCA2 germline mutations were not previously reported to be associated with pleomorphic sarcoma. BRCA2 loss-of-heterozygosity was found in the tumor, resulting in a complete BRCA2 loss-of...
Background
Little information is currently available concerning young medical students desire to pursue a career in oncology, or their career expectations. Methods
This project is a cross-sectional epidemiological study. A voluntary and anonymous questionnaire was distributed to all young oncologists studying in France between the 2nd of October 20...
Tyrosine kinase inhibitors (TKIs) used in the treatment of metastatic renal cell carcinoma present high interindividual variability in clinical response and toxicity. In addition, high interindividual variability in pharmacokinetics (PK) of TKIs is observed which could explain therapeutic failure or elevated toxicity in some patients. Monitoring of...
Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3-4 toxicity, then the potential impact of TDM on clinical decision. Consecutive outpatients tr...
Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard Department of Medical Oncology, Hopital Cochin AP-HP, Paris, France Abstract: Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor recepto...
Le thème de l’AACR de cette année était « Delivering Cures through Cancer Science ». Le sujet vise à renforcer le lien entre la recherche et les progrès réalisés dans le domaine du soin des patients. Un programme multidisciplinaire présenté en cinq jours (du 16 au 20 avril) couvrait tous les domaines de la science du cancer. Au-delà de la session p...
Introduction: Sunitinib, a potent multi-tyrosine kinase (TK) inhibitor, is a standard first-line treatment for metastatic renal cell carcinoma (mRCC). In addition to its antiangiogenic activity, sunitinib is known to have immune-modulating properties especially on regulatory T-cells and tumor-infiltrating lymphocytes. However, data is sparse about...
Background:
Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporad...
The TAT (Targeted Anticancer Therapies) Congress Conference was held in Paris, March 2–4 2015. Once again immunotherapy had the place of honor with PD-1/PD-L1 inhibitors, CSF-1 receptor inhibitor, adoptive immunotherapy, and development of combinations. The challenge is to identify the patients who could best respond to the immunotherapies. Among o...
Background:
Sunitinib is a protein tyrosine kinase (PTK) inhibitor that has immune-modulating properties. In this context, peripheral blood mononuclear cells (PBMC), mainly constituted by lymphocytes, could be a perfect surrogate tissue for identifying and assaying pharmacodynamic biomarkers of sunitinib. In this study, we investigated the changes...
Introduction:
MBC cancer patients may have prolonged survival, and MBC cancers can be considered as a chronic disease. The main goal of the present study was to describe the clinico-biological features of patients surviving more than two years with MBC.
Method: During 4 months, we conducted a national multicentric survey about patients aged ≥ 18 in...
Aim: R/M cancer patients may have prolonged survival, and R/M cancer can be considered as a chronic disease. To our knowledge, there are few data describing these patients. The main goal of the present study was to describe the clinico-biological features of patients surviving more than two years with R/M cancer.
Methods: During 4 months, we conduc...
Major innovations about targeted anticancer therapies were discussed during the TAT 2014 congress, in Washington, March 5-7, 2014. Dr Patricia M. LoRusso (Detroit), one of the most productive oncology phase 1 investigators, introduced the congress with her speech about "The Changing Landscape of Early Phase Trials." Then, various presentations on a...
Sorafenib, a multi-kinase inhibitor that targets the VEGF, PDGF and BRAF pathways, has demonstrated significant clinical activity in metastatic differentiated thyroid cancer. However, all patients eventually experience disease progression with a median progression-free survival close to 10 months. Since sorafenib exposure is known to decrease over...
Citations
... Twenty million new cases of cancer are diagnosed each year, and ten million people die from it. Women account for nine million of these cases and 4.4 million deaths globally each year [1]. According to the World Health Organization, breast cancer will be the most prevalent and deadly cancer in women in 2020, accounting for more than two million new cases and 684,996 deaths annually. ...
... A number of studies are also currently evaluating PARPi in the maintenance therapy of endometrial cancer. In particular, ROCSAN is a multicenter, randomized, open-label, integrated phase 2/3 study comparing the efficacy of niraparib or niraparib plus dostarlimab vs. chemotherapy for the treatment of endometrial/ovarian carcinosarcoma after at least one line of platinum-based chemotherapy [299]. After the phase 2, patients with recurrent or progressing endometrial or ovarian cancer, following at least a first line of platinum-based chemotherapy, are being randomized to receive either niraparib as monotherapy or niraparib in combination with dostarlimab or standard chemotherapy (paclitaxel, doxorubicine, gemcitabine, and topotecan). ...
... A recent pooled analysis of data from 7 clinical trials demonstrated consistent PFS benefits across many clinicopathological subgroups of interest and reaffirmed the addition of CDK4/6 inhibitors to ET in the first and second lines of therapy for HR+/HER2− MBC [17]. Several observational studies published in recent years have assessed utilization patterns of CDK4/6 inhibitors overall and/or by therapy line [18][19][20][21]. However, it remains unknown whether the introduction of CDK4/6 inhibitors has resulted in achieving the therapeutic goal of delaying chemotherapy initiation. ...
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... The risk of hospitalization and death with metabolic associated/nonalcoholic fatty liver disease (MAFLD/NAFLD) severity [301][302][303][304][305][306][307][308], ICU [291,308], MV [291], death [309] ICU [307], death [291,[308][309][310] alcohol-related liver disease (ALD) death [299,310] severity [299] immune-mediated inflammatory disease (IMID)/autoimmune disease hospitalization [311], severity [312] severity [313,314], MV [315], death [313][314][315][316][317] rheumatoid arthritis (RA) hospitalization [288], severity [201,290], death [280,281,288] severity [318,319], ICU [319], MV [319], death [201,318,319] immunosuppression hospitalization [320,321], severity [322], ICU [323], death [13,280,281,321,[324][325][326] hospitalization [320,321], severity [327], MV [315], death [315,321,323,326] organ transplant hospitalization [328], severity [269,329], ICU [323,330], death [201,280,281,329,331] severity [332,333], death [323,330,[334][335][336][337] asplenia death [281] death [280,281,338] cognitive disorder severity [339], death [ COVID-19 have both been associated with cancer [201,208,209,395]. Hematologic [280,281,395,396] and lung cancers [397], and cancers with advanced/metastatic stages [397,398] may have the strongest effect. In addition to the direct effects of cancer, anticancer therapy (chemotherapy, immunotherapy, radiotherapy) might also influence COVID-19 outcomes [394]. ...
... There are only three studies covering patients with breast cancer [15][16][17]. Previous studies have shown that the mortality rate is lower in patients with breast cancer [15]. ...
... Another topic yet to be clarified is the actual relationship between COVID-19 and breast cancer in order to define the level of patients' risk and include it in decision making. The existing literature suggests that breast cancer per se is not a major contributor to COVID-19 mortality, nor is its treatment, and COVID-19 infection outcomes in these patients are mostly affected by patient's comorbidities [7,14,30]. Thus, it would be reasonable to redefine the existing modifications or the population that they concern, considering their application only for high-risk patients. ...
... 21 There is a variation in studies on the mortality rate of this population from 18% to 61%. 22,30 Metastatic neoplasms proportionally increase this statistic. Studies still cite that there is a difficulty in isolating the factor that leads to the prognosis of patients with cancer with COVID-19, since many have advanced neoplasms, not only being SAR-CoV-2 infection a factor for a poor prognosis, but an additional factor to the neoplasia accompanied. ...
... Absolute numbers of circulating neutrophils are commonly elevated in cancers generally, where higher numbers are associated with shorter survival [13,[54][55][56][57]. Several recent reviews together make a strong empirical case for important growth promotion by neutrophils in the common cancers [13,[57][58][59][60][61][62][63][64][65]. However, in addition to the relative numbers to lymphocytes, the NLR seems to be determinative even in presence of non-elevated absolute neutrophil numbers. ...
... In our statistical analysis, sarcopenia was not a significant factor for predicting irAEs, which was similar to our previous report (40) and other studies (16,18,27). However, previous study found that patients with sarcopenia experienced significantly increased risk of irAEs (22,41). It is generally believed that sarcopenia has been associated with a greater incidence of chemotherapy toxicity, but the impact of sarcopenia on irAEs remains controversial. ...
... For the study of TIME signatures, four signatures of (1) IFN-γ signature; (2) GEP score; (3) T cell markers; (4) Chemokines were achieved using a specific set of genes (Supplemental Table 2) with relevant biological function, respectively [23,24]. The GEP score was calculated as a weighted linear average of the constituent genes while the remaining signatures were calculated as the arithmetic means of the corresponding gene [23]. ...
