Publications by authors named "Delphine Loirat"

25 Publications

  • Page 1 of 1

Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.

N Engl J Med 2021 04;384(16):1529-1541

From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.).

Background: Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.

Methods: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases.

Results: A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment.

Conclusions: Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2028485DOI Listing
April 2021

Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients.

Breast Cancer Res 2021 Mar 6;23(1):31. Epub 2021 Mar 6.

Circulating Tumor Biomarkers Laboratory, Inserm CIC-BT 1428, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005, Paris, France.

Background: Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency.

Methods: ER+ HER2- MBC patients were included in a prospective observational cohort before treatment initiation. Tumor response was assessed by radiological evaluation (RECIST v1.1) every 3 months. Plasma samples were collected before treatment (baseline), at day 15 (D15), at day 30 (D30), and at disease progression. We searched for somatic mutations from archived tumor tissues by targeted deep sequencing. For patients with somatic mutations identified, circulating tumor DNA (ctDNA) was tracked using digital droplet PCR. Ratios of ctDNA levels ([D15/baseline] and [D30/baseline]) were then correlated with prospectively registered patient characteristics and outcomes.

Results: Twenty-five of the 61 patients enrolled had a somatic mutation testable in plasma (N = 21, N = 2, N = 2). At baseline, 84% of patients had detectable ctDNA levels but ctDNA levels had no prognostic impact on PFS (p = 0.10). Among those patients, ctDNA was still detected in 82% at D15 and 68% at D30. ctDNA clearance observed at day 30 was associated with longer PFS (HR = 7.2, 95% CI = 1.5-32.6, p = 0.004). On the contrary, a [D30/baseline] ctDNA ratio > 1 was associated with a shorter PFS (HR = 5.1, 95% CI = 1.4-18.3, p = 0.02) and all 5 patients with increased ctDNA levels at D30 showed disease progression after 3 months under palbociclib-fulvestrant. Finally, at the time of radiological tumor progression, ctDNA was detected in all patients tested.

Conclusion: Our study demonstrates that the efficiency of palbociclib and fulvestrant can be monitored by serial analyses of ctDNA before radiological evaluation and that early ctDNA variation is a prognostic factor of PFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-021-01411-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937332PMC
March 2021

Safety, Antitumor Activity, and T-cell Responses in a Dose-Ranging Phase I Trial of the Oncolytic Peptide LTX-315 in Patients with Solid Tumors.

Clin Cancer Res 2021 May 4;27(10):2755-2763. Epub 2021 Feb 4.

Lytix Biopharma, Oslo, Norway.

Purpose: LTX-315 is a first-in-class, 9-mer membranolytic peptide that has shown potent immunomodulatory properties in preclinical models. We conducted a phase I dose-escalating study of intratumoral LTX-315 administration in patients with advanced solid tumors.

Patients And Methods: Thirty-nine patients were enrolled, receiving LTX-315 injections into accessible tumors. The primary objective was to assess the safety and tolerability of this approach, with antitumor and immunomodulatory activity as secondary objectives. Tumor biopsies were collected at baseline and posttreatment for analysis of immunologic parameters.

Results: The most common treatment-related grade 1-2 adverse events were vascular disorders including transient hypotension (18 patients, 46%), flushing (11 patients, 28%), and injection site reactions in 38% of patients. The most common grade 3 LTX-315-related toxicities were hypersensitivity or anaphylaxis (4 patients, 10%). Analysis of immune endpoints in serial biopsies indicated that LTX-315 induces necrosis and CD8 T-cell infiltration into the tumor microenvironment. Sequencing of the T-cell receptor repertoire in peripheral blood identified significant expansion of T-cell clones after treatment, of which 49% were present in available tumor biopsies after treatment, suggesting that they were tumor associated. Substantial volume reduction (≥30%) of injected tumors occurred in 29% of the patients, and 86% (12/14 biopsies) had an increase in intralesional CD8 T cells posttreatment. No partial responses by immune-related response criteria were seen, but evidence of abscopal effect was demonstrated following treatment with LTX-315.

Conclusions: LTX-315 has an acceptable safety profile, is clinically active, induces changes in the tumor microenvironment and contributes to immune-mediated anticancer activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-3435DOI Listing
May 2021

Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial.

Br J Cancer 2021 Mar 21;124(7):1207-1213. Epub 2021 Jan 21.

Department of Medical Oncology, Institut Curie, Paris, France.

Background: CirCe01 trial aimed to assess the clinical utility of circulating tumour cell (CTC)-based monitoring in metastatic breast cancer (MBC) patients beyond the third line of chemotherapy (LC).

Methods: CirCe01 was a prospective, multicentre, randomised trial (NCT01349842) that included patients with MBC after two systemic LC. Patients with ≥5 CTC/7.5 mL (CellSearch®) were randomised between the CTC-driven and the standard arm. In the CTC arm, changes in CTC count were assessed at the first cycle of each LC; patients in whom CTC levels predicted early tumour progression had to switch to a subsequent LC.

Results: Greater than or equal to 5 CTC/7.5 mL were observed in N = 101/204 patients. In the CTC arm (N = 51), 43 (83%) and 18 (44%) patients completed CTC monitoring in the third and fourth lines, respectively, and 18 (42%) and 11 (61%) of these patients, respectively, had no CTC response. Thirteen (72%) and 5 (46%) of these patients underwent early switch to the next LC. Overall survival was not different between the two arms (hazard ratio = 0.95, 95% confidence interval = [0.6;1.4], p = 0.8). In subgroup analyses, patients with no CTC response who switched chemotherapy experienced longer survival than patients who did not.

Conclusions: Due to the limited accrual and compliance, this trial failed to demonstrate the clinical utility of CTC monitoring.

Clinical Trial Registration: NCT, NCT01349842, https://clinicaltrials.gov/ct2/show/NCT01349842 , registered 9 May 2011.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-020-01227-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007590PMC
March 2021

Characteristics and outcome of breast cancer-related microangiopathic haemolytic anaemia: a multicentre study.

Breast Cancer Res 2021 Jan 19;23(1). Epub 2021 Jan 19.

Department of Medical Oncology, Institut Curie, Paris and Saint Cloud, France.

Background: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA.

Methods: Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records.

Results: Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin < 8.0 g/dL (OR = 3.7 [0.9; 16.7]) and prothrombin time < 50% (OR = 9.1 [1.2; 50.0]). A score to predict early death displayed a sensitivity of 86% (95% CI [0.67; 0.96]), a specificity of 73% (95% CI [0.52; 0.88]) and an area under the curve of 0.90 (95% CI [0.83; 0.97]).

Conclusions: Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-021-01386-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814553PMC
January 2021

Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour.

Eur J Cancer 2020 12 5;141:162-170. Epub 2020 Nov 5.

Institut Claudius Regaud, Département D'Oncologie Médicale, Toulouse, France.

Objectives: This study investigated the safety, clinical activity and patient-reported outcomes of patients with diffuse-type tenosynovial giant-cell tumour (dTGCT) of the soft tissue who were treated with emactuzumab, a humanised anti-colony stimulating factor 1 receptor (CSF1R) monoclonal antibody and were followed up for up to 2 years after the start of treatment.

Methods: In this open-label phase 1 study (ClinicalTrials.govNCT01494688), patients received intravenous (IV) emactuzumab from 900 to 2000 mg every two weeks in the dose-escalation phase and at the optimal biological dose of 1000 mg with different schedules in the dose-expansion phase. Adverse event (AE) rates and biomarker assessments from tumour biopsies were analysed. Quality of life was assessed using a standard questionnaire (EuroQol-5D-3L) and the WOMAC® 3.1 Osteoarthritis Index. Tumour responses were determined with magnetic resonance imaging.

Results: Altogether, 63 patients were enrolled into the study. The most frequently reported AEs were pruritus, asthenia and oedema. In 36 patients for whom biopsy tissue was available a substantial decrease of CSF1R-positive and CD68/CD163-positive macrophages was detected. The independently reviewed best overall objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors version 1.1) was 71%. Responses were durable, and an ORR of 70% and 64% was determined after one or two years after enrolment into the study. Clinical activity was accompanied by an improvement in EuroQol-5D-3L and particularly the joint disorder-specific WOMAC score.

Conclusions: Systemic therapy of dTGCT patients with emactuzumab resulted in pronounced and durable responses associated with symptomatic improvement and a manageable safety profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.09.038DOI Listing
December 2020

Efficacy of Circulating Tumor Cell Count-Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: The STIC CTC Randomized Clinical Trial.

JAMA Oncol 2021 Jan;7(1):34-41

Department of Medical Oncology, Institut Curie, Université de Paris, Paris, France.

Importance: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).

Objective: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment.

Interventions: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator.

Design, Setting, And Participants: In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019.

Main Outcome And Measures: The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio.

Results: Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years [64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm]; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09).

Conclusions And Relevance: This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor-positive, ERBB2-negative metastatic breast cancer.

Trial Registration: ClinicalTrials.gov Identifier: NCT01710605.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2020.5660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645742PMC
January 2021

Adjuvant Trastuzumab Emtansine (T-DM1) and Concurrent Radiotherapy for Residual Invasive HER2-positive Breast Cancer: Single-center Preliminary Results.

Am J Clin Oncol 2020 12;43(12):895-901

Departments of Radiation Oncology.

Objectives: The treatment of nonmetastatic HER2-positive breast cancer with residual invasive disease using concurrent Trastuzumab emtansine (T-DM1) and radiotherapy appears to be an effective option. Our aim was to evaluate the acute side effects of this treatment regime.

Methods: Fourteen patients were treated between March 2019 and April 2020 concurrent T-DM1 and radiotherapy. Left ventricular ejection fraction was assessed at baseline, before and after radiotherapy. All toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 3.0.

Results: The median age was 55 years (range 36 to 72). All patients received total dose of 50 Gy for the breast/ chest wall, 10 patients got lymph node irradiation, 4 patients received an additional tumor bed boost. The most common side effect was grade 1 radiodermatitis. A reversible grade 2 left ventricular ejection fraction decrease occurred in 2 patients. During our examination 3 patients showed alanine aminotransferases increase after the cycle 4 of T-DM1, 1 patient had grade 1, 1 patient grade 2, and 1 patient grade 3 alanine aminotransferase increases.

Conclusions: The acute toxicity rate especially focusing on skin and cardiac toxicity were assumed acceptable in our cohort. To safely administer this concomitant treatment, further examination and prospective data are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/COC.0000000000000769DOI Listing
December 2020

Combination of Olaparib and Radiation Therapy for Triple Negative Breast Cancer: Preliminary Results of the RADIOPARP Phase 1 Trial.

Int J Radiat Oncol Biol Phys 2021 Feb 21;109(2):436-440. Epub 2020 Sep 21.

Department of Radiation Oncology, Institut Curie, Paris, France.

Purpose: Preclinical studies have evidenced that triple-negative breast cancer (TNBC) cell lines are more sensitive to poly (ADP-ribose) polymerase inhibitors. This provides a strong rationale for developing a new therapeutic approach for TNBC management based on poly (ADP-ribose) polymerase inhibition. The primary goal of the RADIOPARP phase 1 trial was to evaluate the dose-limiting toxicities (DLT) and the maximum tolerated dose of olaparib combined with locoregional radiation therapy.

Methods And Materials: RADIOPARP was a single institutional phase 1 trial which evaluated olaparib-radiation therapy combination in patients with inflammatory, locoregionally advanced or metastatic TNBC who received neoadjuvant chemotherapy. Radiation therapy delivered 50 Gy to the breast or to the chest wall. Lymph nodes could be included in target volumes according to local guidelines. The dose-finding toxicity-based study was conducted in sequential and adaptive Bayesian scheme using the time-to-event continual reassessment method, with 4 olaparib dose levels (50 mg, 100 mg, 150 mg, and 200 mg twice per day).

Results: Twenty-four patients with Eastern Cooperative Oncology Group Performance Status of 0 or 1 were enrolled from September 2017 to November 2019. Twenty-one patients (87.5%) received the olaparib-radiation therapy combination after breast surgery owing to residual disease after neoadjuvant chemotherapy, and the 3 other patients (12.5%) had unresectable tumors which were refractory to neoadjuvant chemotherapy. All patients received full course combination treatment as follows: 4 patients (pts) at 50 mg twice a day, 8 pts at 100 mg twice a day, 7 pts at 150 mg twice a day, and 5 pts at 200 mg twice a day. No DLT was observed.

Conclusions: Olaparib was escalated to the maximum target dose of 200 mg twice a day without DLT. Further follow-up is needed to evaluate the late toxicities. Pending the long-term results of the RADIOPARP trial, we suggest using 200 mg of olaparib twice per day for future trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.09.032DOI Listing
February 2021

Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy.

Breast Cancer Res 2020 09 14;22(1):98. Epub 2020 Sep 14.

Department of Medical Oncology, Institut Curie, Saint-Cloud, 92210, Paris, France.

Purpose: Previous cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2- MBC patients treated with endocrine therapy and CDK4/6 inhibitor.

Experimental Design: Patients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2- MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden).

Results: From May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0-14). Median follow-up was 13.8 months (range 6-31), with median PFS and OS of 9.6 months (95%CI [7.0-11.3]) and 28 months (95%CI [23-not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20-27,312 Du/L, IQR [89-853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1-1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2-1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3-2], p < 0.0001). That survival prediction was significantly improved by the addition of baseline pTKa to clinicopathological characteristics. Adding pTKa changes at 4 weeks to baseline pTKa did not further increase survival prediction.

Conclusion: This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2- MBC patients treated with endocrine therapy and palbociclib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-020-01334-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489000PMC
September 2020

Fine-needle aspiration as an alternative to core needle biopsy for tumour molecular profiling in precision oncology: prospective comparative study of next-generation sequencing in cancer patients included in the SHIVA02 trial.

Mol Oncol 2021 01 15;15(1):104-115. Epub 2020 Sep 15.

Department of Radiology, Institut Curie, PSL Research University, Paris & Saint-Cloud, France.

High-throughput molecular profiling of solid tumours using core needle biopsies (CNB) allows the identification of actionable molecular alterations, with around 70% success rate. Although several studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to the sensitivity of the less invasive fine-needle aspiration (FNA) compared to CNB to detect molecular alterations. We aimed to prospectively evaluate the potential of FNA to detect such alterations in various tumour types as compared to CNB in cancer patients included in the SHIVA02 trial. An in-house amplicon-based targeted sequencing panel (Illumina TSCA 99.3 kb panel covering 87 genes) was used to identify pathogenic variants and gene copy number variations (CNV) in concomitant CNB and FNA samples obtained from 61 patients enrolled in the SHIVA02 trial (NCT03084757). The main tumour types analysed were breast (38%), colon (15%), pancreas (11%), followed by cervix and stomach (7% each). We report 123 molecular alterations (85 variants, 23 amplifications and 15 homozygous deletions) among which 98 (80%) were concordant between CNB and FNA. The remaining discordances were mainly related to deletions status, yet undetected alterations were not exclusively specific to FNA. Comparative analysis of molecular alterations in CNB and FNA showed high concordance in terms of variants as well as CNVs identified. We conclude FNA could therefore be used in routine diagnostics workflow and clinical trials for tumour molecular profiling with the advantages of being minimally invasive and preserve tissue material needed for diagnostic, prognostic or theranostic purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782085PMC
January 2021

Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.

Nat Commun 2020 06 29;11(1):3272. Epub 2020 Jun 29.

Institut Curie, PSL Research University, INSERM U932, F-75005, Paris, France.

Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17046-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324591PMC
June 2020

Modernizing adverse events analysis in oncology clinical trials using alternative approaches: rationale and design of the MOTIVATE trial.

Invest New Drugs 2020 12 7;38(6):1879-1887. Epub 2020 May 7.

Department of Biostatistics, Institut Claudius Regaud - IUCT-O, 1 avenue Irène Joliot-Curie, 31059, Toulouse Cedex 9, France.

In oncology clinical research, the analysis and reporting of adverse events is of major interest. A consistent depiction of the safety profile of a new treatment is as crucial in establishing how to use it as its antitumor activity. The advent of new therapeutics has led to major changes in the management of patients and targeted therapies or immune checkpoint inhibitors are administered continuously for months or even years. However, the classical methods of adverse events analysis are no longer adequate to properly assess their safety profile. Indeed, the worst grade method and time-to-event analysis cannot capture the duration or the evolution of adverse events induced by extended treatment durations. Many authors have highlighted this issue and argue that the analysis of safety data from clinical trials should be modernized by considering the dimension of time and the recurrent nature of adverse events. This paper aims to illustrate the limitations of current methods and discusses the value of alternative approaches such as the prevalence function, Q-TWiST, the ToxT and the recurrent event approaches. The rationale and design of the MOTIVATE trial, which aims to model the evolution of toxicities over time using the prevalence function in patients treated by immunotherapy, is also presented ( ClinicalTrials.gov Identifier: NCT03447483; Date of registration: 27 February 2018).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-020-00938-xDOI Listing
December 2020

The fully synthetic glycopeptide MAG-Tn3 therapeutic vaccine induces tumor-specific cytotoxic antibodies in breast cancer patients.

Cancer Immunol Immunother 2020 May 7;69(5):703-716. Epub 2020 Feb 7.

Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, 28 rue du Dr Roux, 75015, Paris, France.

Cancer is one of the main causes of mortality worldwide and a major public health concern. Among various strategies, therapeutic vaccines have been developed to stimulate anti-tumoral immune responses. However, in spite of extensive studies, this approach suffers from a lack of efficacy. Recently, we designed the MAG-Tn3 vaccine, aiming to induce antibody responses against Tn, a tumor-associated carbohydrate antigen. The Tn antigen is of interest because it is expressed by several adenocarcinomas, but not normal cells. The fully synthetic glycopeptide vaccine MAG-Tn3 is composed of four arms built on three adjacent Tn moieties associated with the tetanus toxin-derived peptide TT CD4 T-cell epitope. This promiscuous CD4 T-cell epitope can bind to a wide range of HLA-DRB molecules and is thus expected to activate CD4 T-cell responses in a large part of the human population. The MAG-Tn3 vaccine was formulated with the GSK-proprietary immunostimulant AS15, composed of CpG7909, MPL, and QS21, which has been shown to stimulate both innate and humoral responses, in addition to being well tolerated. Here, seven patients with localized breast cancer with a high-risk of relapse were immunized with the MAG-Tn3 vaccine formulated with AS15. The first results of phase I clinical trial demonstrated that all vaccinated patients developed high levels of Tn-specific antibodies. Moreover, these antibodies specifically recognized Tn-expressing human tumor cells and killed them through a complement-dependent cytotoxicity mechanism. Overall, this study establishes, for the first time, the capacity of a fully synthetic glycopeptide cancer vaccine to induce specific immune responses in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-020-02503-0DOI Listing
May 2020

Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial.

JCO Precis Oncol 2018 19;2. Epub 2018 Oct 19.

, , , , , , , , , , , , , , , , , and , Institut Curie, Paris; , , , , , , , , , , , , , and , Institut Curie; , Institut National de la Santé et de la Recherche Médicale U900 Research Unit, Saint-Cloud; , Institut Paoli-Calmettes, Marseille; , Centre Léon Bérard, Lyon; , Centre Alexis Vautrin, Nancy; , Institut Claudius Régaud, Toulouse; , Centre René Gauducheau, Nantes; , Centre Georges-François Leclerc, Dijon; and , Versailles-Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France.

Purpose: Precision medicine trials constitute a precious source of molecular data with prospective clinical annotations allowing the exploration of patients' subpopulations according to specific clinical or biological questions. Using the SHIVA01-the first randomized trial comparing molecularly targeted therapy on the basis of tumor molecular profiling versus conventional chemotherapy in metastatic cancer patients who failed standard of care therapy-annotated database, we report cases of patients treated in the trial with targeted therapy who experienced an objective response or prolonged disease stabilization in light of patients' molecular alterations.

Patients And Methods: We selected all patients included in SHIVA01 treated with a molecularly targeted agent (MTA) who experienced an objective response or disease stabilization that lasted longer than 6 months according to Response Evaluation Criteria in Solid Tumors version 1.1.

Results: Among the 170 patients who received MTAs in the SHIVA01 trial, 15 patients (9%) experienced an objective response (n = 3) or disease stabilization that lasted longer than 6 months (n = 12). The most frequent histologic subtypes were breast cancer (27%) and cervical cancer (20%). Six patients, including three patients with breast cancer, were treated with abiraterone on the basis of androgen receptor protein overexpression. Five patients were treated with everolimus on the basis of a heterozygous deletion with loss of protein expression, mutation, or both alterations. The remaining four patients were treated with tamoxifen, erlotinib, imatinib, and vemurafenib on the basis of progesterone receptor expression, amplification, mutation, and mutation, respectively. mutations were absent in responder patients.

Conclusion: Analysis of patients who experienced objective responses or disease stabilization that lasted longer than 6 months allowed the identification of potential biomarkers of sensitivity and resistance to MTAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/PO.18.00048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450915PMC
October 2018

Disseminated Tumor Cells Predict Efficacy of Regional Nodal Irradiation in Early Stage Breast Cancer.

Int J Radiat Oncol Biol Phys 2019 02 4;103(2):389-396. Epub 2018 Oct 4.

Department of Medical Oncology, Institut Curie, PSL Research University, Paris and Saint Cloud, France; Circulating Tumor Biomarkers Laboratory, Siric, Institut Curie, PSL Research University, Paris, France; UVSQ, Paris Saclay University, Paris, France.

Purpose: Disseminated tumor cells (DTCs) collect in the bone marrow and indicate micrometastatic spread. We previously reported that DTCs could be a predictive factor for the efficacy of regional node irradiation (internal mammary nodes [IMNs]/supra- and infraclavicular nodes [SCNs]). In this article, we report the long-term results (>10 years) on the impact of DTC status in early stage breast cancer.

Methods And Materials: Patients with localized breast cancer were eligible for inclusion in this prospective cohort. DTCs were obtained from a medullary iliac crest sample performed before any primary therapy. DTC status was prospectively assessed by pathologists. Irradiation volumes were defined per standard of care. Cumulative incidence rates and hazard ratios were obtained using both Cox and Fine-Gray models. Interaction tests were performed to confirm the predictive value of DTC status in a multivariate analysis.

Results: Six hundred twenty patients with localized breast cancer were included. Overall, 94 patients (15.2%) were DTC-positive. After a median follow-up of 11.7 years, 47 patients (7.6%) experienced locoregional relapse. DTC detection was associated with a higher risk of locoregional relapse in univariate and multivariate analyses (Cox hazard ratio, 3.26; 95% confidence interval, 1.6-5.7; P = .001). In the multivariate subgroup analysis, IMN/SCN irradiation significantly reduced locoregional relapse among DTC-positive patients compared with DTC-negative patients (interaction test: hazard ratio, 0.3; 95% confidence interval, 0.1-0.9; P = .02). IMN/SCN was the only irradiation volume with an impact on locoregional relapse in patients according to DTC status, and the predictive value of DTC status for the benefit of locoregional irradiation was independent of locoregional nodal status.

Conclusions: This long-term analysis confirms the predictive impact of DTC status on the efficacy of regional radiation therapy for locoregional relapse in early breast cancer. After further studies, DTC status could be used as a decision tool to better tailor adjuvant radiation therapy in patients with early stage breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.09.033DOI Listing
February 2019

Relevance of a molecular tumour board (MTB) for patients' enrolment in clinical trials: experience of the Institut Curie.

ESMO Open 2018 6;3(3):e000339. Epub 2018 Apr 6.

Department of Radiology and Nuclear Medicine, Institut Curie, PSL Research University, Paris, France.

Background: High throughput molecular screening techniques allow the identification of multiple molecular alterations, some of which are actionable and can be targeted by molecularly targeted agents (MTA). We aimed at evaluating the relevance of using this approach in the frame of Institut Curie Molecular Tumor Board (MTB) to guide patients with cancer to clinical trials with MTAs.

Patients And Methods: We included all patients presented at Institut Curie MTB from 4 October 2014 to 31 October 2017. The following information was extracted from the chart: decision to perform tumour profiling, types of molecular analyses, samples used, molecular alterations identified and those which are actionable, and inclusion in a clinical trial with matched MTA.

Results: 736 patients were presented at the MTB. Molecular analyses were performed in 442 patients (60%). Techniques used included next-generation sequencing, comparative genomic hybridisation array and/or other techniques including immunohistochemistry in 78%, 51% and 58% of patients, respectively. Analyses were performed on a fresh frozen biopsy in 91 patients (21%), on archival tissue (fixed or frozen) in 326 patients (74%) and on both archival and fresh frozen biopsy in 25 patients (6%). At least one molecular alteration was identified in 280 analysed patients (63%). An actionable molecular alteration was identified in 207 analysed patients (47%). Forty-five analysed patients (10%) were enrolled in a clinical trial with matched MTA and 29 additional patients were oriented and included in a clinical trial based on a molecular alteration identified prior to the MTB analysis. Median time between date of specimen reception and molecular results was 28 days (range: 5-168).

Conclusions: The implementation of an MTB at Institut Curie enabled the inclusion of 10% of patients into a clinical trial with matched therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/esmoopen-2018-000339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890857PMC
April 2018

Cost analysis of adverse events associated with non-small cell lung cancer management in France.

Clinicoecon Outcomes Res 2017 27;9:443-449. Epub 2017 Jul 27.

Institut Gustave Roussy, Villejuif, France.

Background: Adverse events (AEs) related to medical treatments in non-small cell lung cancer (NSCLC) are frequent and need an appropriate costing in health economic models. Nevertheless, data on costs associated with AEs in NSCLC are scarce, particularly since the development of immunotherapy with specific immune-related AEs.

Objective: To estimate the costs of grades 3 and 4 AEs related to NSCLC treatments including immunotherapy in France.

Methods: Grades 3 and 4 AEs related to treatment and reported in at least 1% of patients in Phase III clinical trials for erlotinib, ramucirumab plus docetaxel, docetaxel, pemetrexed plus carboplatin plus bevacizumab, platinum-based chemotherapies, nivolumab and pembrolizumab were identified. When no cost evaluation was reported in literature, estimates on standard treatments and medical resource use for each AE were obtained thanks to an expert panel. Total cost per AE was calculated from a French national health insurance perspective and updated in 2017 Euros. Hospital stay costs were estimated based on public and private weighted tariffs and data from the French Medical Information System (Programme de Médicalisation des Systèmes d'Information). Costs of tests, consultations and treatments were calculated based on national reimbursement tariffs.

Results: Overall, costs of grades 3 and 4 AEs related to treatment ranged from €46 per event to €7,742 per year. Fourteen out of 24 AEs identified had a mean estimated cost over €2,000. The highest mean costs were related to type 1 diabetes (€7,742 per year) followed by pneumonitis (€5,786 per event), anemia (€5,752 per event), dehydration (€5,207 per event) and anorexia (€4,349 per event). Costs were mostly driven by hospitalization costs.

Conclusion: Among the AEs identified, a majority appeared to have an important economic impact, with a management cost of at least €2,000 per event mainly driven by hospitalization costs. This study may be of interest for economic evaluations of new interventions in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CEOR.S138963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538537PMC
July 2017

Circulating tumor cells: clinical validity and utility.

Int J Clin Oncol 2017 Jun 25;22(3):421-430. Epub 2017 Feb 25.

Department of Medical Oncology, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005, Paris, France.

Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-017-1105-2DOI Listing
June 2017

[Cell cycle inhibitors in endocrine receptor positive breast cancer].

Bull Cancer 2017 Feb 23;104(2):114-122. Epub 2017 Jan 23.

Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France.

Dysregulation of cellular cycle is a key component of carcinogenesis and its targeting represents an interesting approach. Recently, the development of selective inhibitors of the cycle targeting the cyclin-dependent kinases (CDK) 4 and 6 revived interest in this therapeutic class after the failure of pan-inhibitors. Palbociclib, ribociclib, and abemaciclib are the 3 drugs with the most advanced development. They demonstrated preclinical activity in luminal breast cancer models and are under clinical evaluation. The first available studies demonstrate the value of these compounds with an improved prognosis of metastatic patients in combination with endocrine therapy (palbociclib, ribociclib) or in monotherapy (abemaciclib). The results of ongoing studies will clarify the role of these agents in our new strategies and the individualisation of biomarkers will help to define patients who benefit most from this approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2016.12.005DOI Listing
February 2017

Loss of immune tolerance to IL-2 in type 1 diabetes.

Nat Commun 2016 10 6;7:13027. Epub 2016 Oct 6.

Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris 75005, France.

Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms13027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059699PMC
October 2016

Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.

Eur J Cancer 2016 10 15;66:75-82. Epub 2016 Aug 15.

Department of Neurology, OncoNeuroTox Center, Paris, France; Department of Neurology, Val-de-Grâce Teaching Hospital, Service de Santé des Armées, 74, boulevard de Port Royal, 75005 Paris, France; Department of Neurology, Cognition an Action Group (COGNAC-G) UMR 8257 Centre National de la Recherche Scientifique, Service de Santé des Armées, Paris Descartes University, 45, rue des Saints-Pères, 75006 Paris, France.

Background: Despite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities.

Methods: This retrospective, multi-centre study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8 weeks after termination of treatment and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded.

Results: Thirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (n = 18), PRES (n = 9), TIA (n = 6) or haemorrhagic stroke (n = 1). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (n = 6), severe vascular toxicity recurred in two patients.

Conclusions: Neurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2016.07.008DOI Listing
October 2016

[Management of the cutaneous side effects of chemotherapies and targeted therapies].

Soins 2015 Jun(796):17-24

Département d'oncologie médicale, Institut Curie, 26, rue d'Ulm, 75005 Paris, France; Translational Immunotherapy Team- Inserm U932/Département de transfert, Institut Curie, 26, rue d'Ulm, 75005 Paris, France. Electronic address:

The treatments used in oncology cause frequent cutaneous side effects. The different types of cutaneous toxicities depend on the class of anti-tumour therapies and can involve the skin, mucosa, nails and hair. Effectively managing these cutaneous toxicities requires adapted preventive and curative measures in order to reduce their impact, notably on patients' quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soin.2015.04.002DOI Listing
June 2015

[Immunotherapies and targeted therapies in medical oncology].

Bull Cancer 2014 Jan;101(1):31-9

Gustave-Roussy, université Paris-Sud, DITEP, département des innovations thérapeutiques et des essais précoces, 114, rue Édouard-Vaillant, 94800 Villejuif, France.

New immunotherapies, also called "immune checkpoints", are promising and showed interesting antitumoral activities in particular in advanced setting of melanoma, clear cell renal cancer or non-small cell lung carcinoma. These treatments include ipilimumab, anti-PD-1 and anti-PD-L1. There is a strong rational for combination of immunotherapies and targeted therapies. This review is dedicated to expose the theorical issues and preclinical data of such combinations. This review examined the impact of immunotherapies on transduction pathways and modification of immunity related to targeted therapies. First clinical data form early drug development studies showed the difficulties observed with such combination and limitating toxicities. Finally, potential interesting combinations are overviewed with an emphasis on sequential treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/bdc.2013.1865DOI Listing
January 2014

A case of daptomycin-induced immune thrombocytopenia.

Antimicrob Agents Chemother 2012 Dec 1;56(12):6430-1. Epub 2012 Oct 1.

Intensive Care Unit, Saint Joseph Hospital Network, Paris, France.

We report a case of severe daptomycin-induced immune thrombocytopenia in a patient treated for methicillin-resistant Staphylococcus epidermidis and ampicillin-resistant Enterococcus faecalis bacteremia acquired in an intensive care unit. Serum antibodies bound to platelets in the presence of daptomycin on flow cytometry. There was no evidence of other causes of thrombocytopenia. The patient died of brain herniation complicating extensive cerebral hemorrhage. To our knowledge, this is the first described case of daptomycin-induced thrombocytopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01787-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497155PMC
December 2012