Jean-Yves Blay

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France

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Publications (317)2130.48 Total impact

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    ABSTRACT: Background The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group – Bone Tumor Study Group (GSF-GETO) national registry. Methods All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. Results Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9–72). The median number of previous lines of chemotherapy was 3 (range 1–8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5 % of patients (95 % Confidence Interval (CI) [20–52.8]). The median Progression-Free Survival (PFS) was 3 months (95 % CI [2–5.4]) for patients treated by sirolimus and 1.8 months (95 % CI [1.3–2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15 %. The median Overall Survival (OS) was 6.8 months (95 % CI [4.7–12.1]), and one-year OS was 24 %. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95 % CI [1.05–7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6 % of cases respectively. Conclusion Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.
    BMC Cancer 12/2015; 15(1). DOI:10.1186/s12885-015-1894-5 · 3.36 Impact Factor
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    ABSTRACT: Epithelioid hemangioendothelioma is a rare connective tissue tumor of vascular origin. It is most commonly found in young to middle aged women, and its clinical behavior is remakably variable from an indolent metastatic tumor to an aggressive rapidly growing neoplasm. Most tumors are diagnosed in an advanced unresectable phase and when clinically aggressive, require systemic cytotoxic treatment of sarcoma. Then, the 5-year survival rate after chemotherapy does not exceed 30%. Antiangiogenics are active in selected sarcoma subtypes: pazopanib, the only anti angiogenic registered agent for sarcoma provides a median PFS of 4.5 months only in the pivotal study. Their activity in EHE has been reported but long term outcome of these patients remain unreported. We report a case of a female patient with HEH who was treated with pazopanib for almost 8 years. Pazopanib therapy resulted in clinical improvement of symptoms and durable stabilization of liver tumors and lung lesions. Conclusion: Pazopanib is a promising therapeutic option in patients with HEH.
    12/2015; 5(1). DOI:10.1186/s13569-014-0018-3
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    ABSTRACT: Angiogenesis, among other signaling pathways, plays a key-role in sarcoma biology. Regorafenib (RE) has recently been shown to be effective in imatinib and sunitinib-refractory GIST in a phase III trial. We are conducting an international trial (France, Austria and Germany) consisting in 4 parallel double-blind placebo-controlled randomized (1/1) phase II trials to assess the activity and safety of RE in doxorubicin-refractory STS ( NCT01900743). Each phase II trial is dedicated to one of the 4 following histological subgroups: liposarcoma, leiomyosarcoma, synovial sarcoma and other sarcoma. Within each randomized trial the following stratification factors will be applied: countries and prior exposure to pazopanib. Key-eligibility criteria are: measurable disease, age ≥18, not > 3 previous systemic treatment lines for metastatic disease, metastatic disease not amenable to surgical resection. The primary endpoint is progression-free survival (PFS) according to central radiological review. Secondary endpoints are: Toxicity (NCI-CTC AE V4.0); time to progression; Growth modulation index in pts receiving RE after randomization; 3 and 6 months PFS-Rates, best response rate and overall survival. Each phase II trial will be separately analyzed. In 3 trials, statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.05 with a total sample size of 192 pts. To take into account the rarity of synovial sarcoma, the statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.2 Tumor assessment is done monthly during the 4 first months, and every 3 months thereafter. After central radiological confirmation of tumor progression, an optional open-label option is offered to eligible patients. The design of this trial allows an assessment of regorafenib activity over placebo in four sarcoma strata and might provide evidence for launching a phase III trial. This study includes both integrative and exploratory translational research program. The study is enrolling since June 2013 (TRIAL REGISTRATION NUMBER: EudraCT N°: 2012-005743-24, on the 15(th) February 2012).
    BMC Cancer 12/2015; 15(1):1143. DOI:10.1186/s12885-015-1143-y · 3.36 Impact Factor
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    ABSTRACT: Purpose: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST). Patients and methods: Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis. Results: A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98.5% CI, 0.50 to 1.25; P = .21); RFS was 84% versus 66% at 3 years and 69% versus 63% at 5 years (log-rank P < .001); and 5-year overall survival was 100% versus 99%, respectively. Among 528 patients with high-risk GIST by local pathologist, 5-year IFFS was 79% versus 73%; among 336 centrally reviewed high-risk patients, it was 77% versus 73%, respectively. Conclusion: This study confirms that adjuvant imatinib has an overt impact on RFS. No significant difference in IFFS was observed, although in the high-risk subgroup there was a trend in favor of the adjuvant arm. IFFS was conceived as a potential end point in the adjuvant setting because it is sensitive to secondary resistance, which is the main adverse prognostic factor in patients with advanced GIST.
    Journal of Clinical Oncology 11/2015; DOI:10.1200/JCO.2015.62.4304 · 18.43 Impact Factor
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    ABSTRACT: Background: Neurofibromatosis type I (NF1) predisposes patients to various neoplasias, including gastrointestinal stromal tumors (GISTs). Little is known about the risk of developing GISTs for NF1 patients or the clinicopathologic features and prognosis of NF1-GIST. Methods: We conducted a multi-detector computed tomography screen for adult NF1 patients between 2003 and 2012. Clinicopathologic data of sporadic GISTs from patients who underwent surgery between 2001 and 2010 were retrospectively collected from 32 hospitals in Japan. Results: CT screening identified 6 GIST patients from the 95 NF1 patients screened, suggesting that the prevalence rate of GISTs was approximately 6.3/100 in NF1 patients. All 6 NF1 patients exhibited hyperplasia of the interstitial cells of Cajal in the adjoining small intestine. NF1-GISTs may account for 1.1-1.3 % of primary sporadic GISTs and present as multiple tumors in the small intestine, with low mitotic activity and no KIT or PDGFRA mutations. The risk of recurrence and mortality is very similar between NF1 and non-NF1 patients after surgical resection of GISTs. Conclusions: NF1 patients may be predisposed to developing small intestinal GISTs, which may appear as multiple GISTs without KIT and PDGFRA mutations. The prognosis of patients with NF1-GISTs is similar to patients with conventional GISTs.
    Journal of Gastroenterology 10/2015; DOI:10.1007/s00535-015-1132-6 · 4.52 Impact Factor
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    ABSTRACT: Background: Tumor genotype plays a crucial role in clinical management of GIST. Whether genetic polymorphism of KIT may influence GIST patient outcome is unclear. Methods: We investigated the biological and clinical significance of the presence of KIT exon 10 variant (c.1621 A > C), KIT (L541) , in a transfected cell line (3 T3 L541) and in two retrospectively collected series of 109 GIST patients in total. The control group consisted of 60 healthy donors collected at the French department of blood transfusion. Results: In the 3 T3 L541 cell line, KIT(L541) protein exhibited a spontaneous phosphorylation status comparable to that of wild-type KIT but displayed a phosphorylation pattern of AKT and ERK1/2 that was found similar to that of the classical mutated forms of the KIT receptor. Of 109 patients enrolled in this retrospective translational research study, 24 (22 %) harboured KIT (L541) , similarly to the control group of healthy donors (n = 10 of 60, 17 %). A higher prevalence of the variant KIT (L541) was observed in patients with metastatic status at diagnosis (KIT (L541) correlated nine of 22 versus 15 of 87, p = 0.02). In addition, patients with KIT (L541) and localized GIST had a higher rate of relapse at 5 years and lower relapse free survival at 5 years in univariate, as well as in multivariate analysis. Response rate and duration of response to imatinib was similar in KIT (L541) and KIT (M541) patients. Conclusion: KIT (L541) genotype is associated with a higher risk of metastasis at diagnosis and a higher risk of relapse in GIST patients.
    BMC Cancer 10/2015; 15(1):780. DOI:10.1186/s12885-015-1817-5 · 3.36 Impact Factor
  • Jean-Yves Blay · Alice Levard ·
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    ABSTRACT: Imatinib mesylate is approved for the adjuvant treatment of KIT-positive gastrointestinal stromal tumor (GIST) following surgical resection. However, uncertainty remains in terms of patient eligibility for adjuvant treatment and the optimal duration of treatment. Here, we present two challenging patient cases encountered in clinical practice that highlight the ambiguity in the current recommendations for adjuvant imatinib in GIST and discuss our approaches and rationales for treatment. The first case involves a 36-year-old man with a 7 cm duodenal GIST and possible tumor rupture during surgical resection. This patient's risk of GIST recurrence was either intermediate or high depending on which risk stratification criteria were used. The patient was treated with adjuvant imatinib for 3 years and experienced disease recurrence 14 months after the completion of treatment. Imatinib treatment was reintroduced, and the patient is in partial response 17 months later. The second case involves a 46-year-old woman at high risk of recurrence following surgical resection. Adjuvant treatment with imatinib was initiated. After considering the patient's initial high risk and good side-effect profile, the decision was made to continue adjuvant imatinib treatment for 5 years. As of May 2013, the patient has been receiving continuous imatinib treatment for 52 months, with no sign of progression. These reports exemplify the challenges faced in clinical practice because of uncertainties in optimal risk stratification criteria and duration of treatment. They stress the importance of individualized treatment and shared decision making between the physician and the patient.
    Anti-cancer drugs 10/2015; 27(1). DOI:10.1097/CAD.0000000000000286 · 1.78 Impact Factor
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    ABSTRACT: Background: Malignant peripheral nerve sheath tumors (MPNST) are one of the most frequent causes of death in patients with neurofibromatosis type 1 (NF1). Early detection is crucial because complete surgical resection is the only curative treatment. It has been previously reported that an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) image with a T/L (Tumor/Liver) SUVmax ratio > 1.5 provides a high negative predictive value; however, it is not specific enough to make a NF1-related MPNST diagnosis. A formal proof of malignant transformation from a histological analysis is necessary before surgical excision because the procedure can cause mutilation. The objective of the present work was to investigate the effectiveness of and complications associated with PET/CT-guided percutaneous biopsies for an NF1-related MPNST diagnosis. Methods: PET/CT-guided percutaneous biopsy procedures performed on 26 NF1 patients with a clinical suspicion of MPNST and a suspect lesion from a PET/CT scan (T/L SUVmax ratio > 1.5) were retrospectively evaluated. The localization of the suspected malignant site was determined using PET/CT. A stereotactic (ultrasonic and CT control) core biopsy technique was used with a local anesthesia. Results: The first PET/CT-guided percutaneous biopsies enabled a pathological diagnosis for all of the patients (no "inconclusive " results were obtained), and no secondary procedures were needed. Among the 26 patients, the histopathological results from the biopsy were malignant in 17 cases and benign (BPNST with atypical cells) in nine cases. No complications from the diagnostic procedure were observed. A surgical resection was performed in 18 patients (seven benign and 11 malignant biopsies), removing the fine needle biopsy scar. In addition, six locally advanced/metastatic MPNST were treated with chemo/radiotherapy, and two BPNST had no progression after a follow-up of 14 and 39 months, respectively. The PET/CT-guided percutaneous biopsy gave 25 accurate diagnoses and one false negative (BPNST with atypical cells on the biopsy and MPNST on the operated tumor), resulting in a diagnostic accuracy rate of 96%. This false negative case may be explained by the high heterogeneity of the tumor: benign areas were contiguous with the malignant ones and associated with inflammation. Conclusions: PET/CT-guided percutaneous biopsies are an effective and relatively non-traumatic procedure for diagnosis of NF1-related MPNST. It is the most reliable approach for early detection of MPNST.
    PLoS ONE 10/2015; 10(10):e0138386. DOI:10.1371/journal.pone.0138386 · 3.23 Impact Factor
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    ABSTRACT: BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; number, NCT01524978.).
    New England Journal of Medicine 08/2015; 373(8):726-36. DOI:10.1056/NEJMoa1502309 · 55.87 Impact Factor
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    ABSTRACT: Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines-for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry-their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.
    Gastric Cancer 08/2015; DOI:10.1007/s10120-015-0526-8 · 3.72 Impact Factor
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    ABSTRACT: Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal sarcomas. This global, prospective registry followed patients with advanced or localised GIST (2007-2011). Current and evolving diagnostics, treatments and outcome measures in patients with GIST were assessed. Eligible patients were diagnosed with advanced or localised GIST within 15months of registry entry. No treatment plan was prescribed, and no visit schedule was mandated. Treating physicians recorded patient information, including tumour response, diagnostic methods, medications, surgeries performed, mutation status and adverse events leading to dose/medication changes. Survival outcomes were estimated using the Kaplan-Meier method. Other data were analysed using descriptive statistics. The registry included 1663 patients (advanced GIST, n=1095; localised GIST, n=537). Medications (e.g. tyrosine kinase inhibitor use and dosing), disease progression or recurrence and physician assessment of response to treatment in registry patients were consistent with controlled trials and prevailing clinical recommendations. In advanced GIST, estimated 30-month progression-free survival (PFS) (59.8%) and overall survival (OS) (82.7%) were higher than results from previously reported trials (≈40% and ≈70%, respectively). Consistent with treatment guidelines, the most common initial treatments were imatinib for advanced GIST, and complete surgical resection for localised GIST. Computed tomography scans were the most common imaging technique used at diagnosis and follow-up. Mutation analysis was performed at diagnosis in only 15.3% and 14.5% of patients with advanced and localised GIST, respectively. In this real-world GIST registry, patients with advanced GIST were treated with imatinib and patients with localised GIST received surgical resection, in accordance with prevailing clinical recommendations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 08/2015; 130(16). DOI:10.1016/j.ejca.2015.07.010 · 5.42 Impact Factor
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    ABSTRACT: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a highly aggressive neoplasm occurring in young females. Paraneoplastic hypercalcaemia is associated in two-third of cases. Recent studies demonstrated that this rare tumor harbors molecular features of a malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT in a 14 year-old girl comprehensively molecularly characterized . We also discuss the invaluable input of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies in routine practice.
    Pediatric and Developmental Pathology 07/2015; DOI:10.2350/15-04-1624-CR.1 · 0.87 Impact Factor
  • Jean-Yves Blay · Eunjuh Hurh · Steven Green · Steven Novick ·

    The Lancet Oncology 07/2015; 16(7). DOI:10.1016/S1470-2045(15)00016-9 · 24.69 Impact Factor
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    ABSTRACT: The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS). Patients were treated with paclitaxel alone (90 mg/m(2) per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug. A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion). The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 07/2015; 33(25). DOI:10.1200/JCO.2015.60.8505 · 18.43 Impact Factor
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    ABSTRACT: Validated predictive biomarkers for multi-tyrosine kinase inhibitors (MTKI) efficacy are lacking. We hypothesized that interindividual response variability is partially dependent on somatic DNA copy number alterations (SCNAs), particularly those of genes encoding the protein tyrosines targeted by MTKI (called target genes). Genomic alterations were investigated in MTKI responsive and non responsive patients with different histological subtypes included in the ProfiLER protocol (NCT 01774409). From March 2013 to August 2014, 58 patients with advanced cancer treated with one of 7 MTKIs were included in the ProfiLER trial and split into one discovery cohort (n = 13), and 2 validation cohorts (n = 12 and 33). An analysis of the copy number alterations of kinase-coding genes for each of 7 MTKIs was conducted. A prediction algorithm (SUMSCAN) based on the presence of specific gene gains (Tumor Target Charge, TTC) and losses (Tumor Target Losses, TTL) was conceived and validated in 2 independent validation cohorts. MTKI sensitive tumors present a characteristic SCNA profile including a global gain profile, and specific gains for target genes while MTKI resistant tumors present the opposite. SUMSCAN favorable patients achieved longer progression-free and overall survival. This work shows that the copy number sum of kinase-coding genes enables the prediction of response of cancer patients to MTKI, opening a novel paradigm for the treatment selection of these patients.
    Oncotarget 07/2015; 6(28). DOI:10.18632/oncotarget.4557 · 6.36 Impact Factor
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    ABSTRACT: Diffuse-type tenosynovial giant cell tumour (dt-GCT) of the soft tissue (alternatively known as pigmented villonodular synovitis), an orphan disease with unmet medical need, is characterised by an overexpression of colony-stimulating factor 1 (CSF1), and is usually caused by a chromosomal translocation involving CSF1. CSF1 receptor (CSF1R) activation leads to the recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage that constitute the tumor mass in dt-GCT. Emactuzumab (RG7155) is a novel monoclonal antibody that inhibits CSF1R activation. We have assessed the safety, tolerability and activity of emactuzumab in patients with Dt-GCT of the soft tissue. In this phase 1, first-in-human dose-escalation and dose-expansion study, eligible patients were aged 18 years or older with dt-GCT of the soft tissue with locally advanced disease or resectable tumours requiring extensive surgery, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease according to Response Evaluation Criteria In Solid Tumors version 1.1, and adequate end-organ function. Patients with GCT of the bone were not eligible. Patients received intravenous emactuzumab at 900 mg, 1350 mg, or 2000 mg every 2 weeks in the dose-escalation phase and at the optimal biological dose in a dose-expansion phase. The primary objective was to evaluate the safety and tolerability of emactuzumab, and to determine the maximum tolerated dose or optimal biological dose. All treated patients were included in the analyses. Expansion cohorts are currently ongoing. This study is registered with, number NCT01494688. Between July 26, 2012, and Oct 21, 2013, 12 patients were enrolled in the dose-escalation phase. No dose-limiting toxicities were noted in the dose-escalation cohort; on the basis of pharmacokinetic, pharmacodynamic, and safety information, we chose a dose of 1000 mg every 2 week for the dose-expansion cohort, into which 17 patients were enrolled. Owing to different cutoff dates for safety and efficacy readouts, the safety population comprised 25 patients. Common adverse events after emactuzumab treatment were facial oedema (16 [64%] of 25 patients), asthenia (14 [56%]), and pruritus (14 [56%]). Five serious adverse events (periorbital oedema, lupus erythematosus [occurring twice], erythema, and dermohypodermitis all experienced by one [4%] patient each) were reported in five patients. Three of the five serious adverse events-periorbital oedema (one [4%]), lupus erythematosus (one [4%]), and dermohypodermitis (one [4%])-were assessed as grade 3. Two other grade 3 events were reported: mucositis (one [4%]) and fatigue (one [4%]). 24 (86%) of 28 patients achieved an objective response; two (7%) patients achieved a complete response. Further study of dt-GCT is warranted and different possibilities, such as an international collaboration with cooperative groups to assure appropriate recruitment in this rare disease, are currently being assessed. F Hoffmann-La Roche. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 07/2015; 16(8). DOI:10.1016/S1470-2045(15)00132-1 · 24.69 Impact Factor
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    ABSTRACT: After the revelation of kinase targeting with orally available small molecules, the use of imatinib in chronic myelogenous leukemia and in gastrointestinal stromal tumor (GIST) has now become commonplace and just two of many examples of the use of kinase inhibitors in cancer. In this article, we discuss important practice points that may impact upon questions of therapy of primary and metastatic GIST, with the hope that the questions addressed in this rare solid tumor can serve as examples of what can be achieved with kinase-directed therapies in other cancers. We present cases that highlight some of the key issues in GIST management and afterward discuss both points of consensus and controversial issues in what is now recognized as one of the most common forms of sarcoma. ©AlphaMed Press.
    The Oncologist 06/2015; 20(7). DOI:10.1634/theoncologist.2014-0471 · 4.87 Impact Factor
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    ABSTRACT: The EDIFICE programme began in 2005 and set out to provide a clearer insight over time into the participation of the French population in cancer screening. EDIFICE 3 was conducted in 2011 by phone interviews among a representative sample of 1603 individuals aged between 40 and 75 years using the quota method. The analysis focused on the target populations (50-74 years) of the national screening programmes for breast and colorectal cancer. The same populations were also assessed with respect to prostate cancer screening. In 2005, 93% of the sample population had undergone at least one mammogram in their lifetime; this figure reached 94% in 2008 and 95% in 2011. Compliance with recommended intervals improved between 2005 and 2011, and significantly so for women aged 65-74 years. In 2005, 25% of respondents reported having undergone at least one colorectal cancer screening test; this figure reached 38% in 2008 and 59% in 2011. Recommended intervals were respected by 30 and 51% in 2008 and 2011, respectively. In 2005, 2008 and 2011, a total of 36, 49 and 50% of men reported having undergone at least one prostate cancer screening test. This rate decreased significantly in men aged 50-59 years between 2008 and 2011 (44 vs. 37%, P≤0.05). Attendance rates in national screening programmes are high and stable for breast cancer, and although currently improving for colorectal cancer, the European guideline target has not yet been reached. Despite the absence of recommendations for prostate cancer screening, participation remains constant.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S68-72. DOI:10.1097/CEJ.0000000000000146 · 3.03 Impact Factor
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    ABSTRACT: One of the current goals of the French national cancer plan is to reduce healthcare inequalities. This study investigated the potential links between vulnerable social status, exposure to lung cancer risk factors and access to healthcare to highlight ways to improve lung cancer control in this population. The nationwide observational study EDIFICE 3 was carried out through phone interviews of a representative sample of 1603 individuals (age 40-75 years). The EPICES validated questionnaire was used to assess and classify vulnerable respondents. The vulnerable population identified represented 33% of the sample. Compared with nonvulnerable individuals, they had more risk factors for cancer: a higher BMI (26.0 vs. 24.8, P≤0.01), 38% were active smokers (vs. 23%, P≤0.01) with a heavier and longer-lasting tobacco consumption (16.0 cigarettes/day vs. 10.1, P≤0.01 and 29.4 vs. 26.3 years of smoking, P≤0.01) and they were less likely to undertake any physical activities (42 vs. 77%, P≤0.01). They also presented more comorbidities (on average 2.2 vs. 1.8, P≤0.01). Access to healthcare, however, was not discriminatory: vulnerable individuals declared consulting a general practitioner or an oncologist more often than the nonvulnerable subgroup (5.4 vs. 3.7 and 6.7 vs. 2.5 consultations in the previous 12 months, respectively, P≤0.01). Because access to healthcare and screening attendance show no signs of discrimination against vulnerable populations, efforts to reduce inequities in lung cancer control should focus on prevention.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S82-6. DOI:10.1097/CEJ.0000000000000143 · 3.03 Impact Factor
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    ABSTRACT: Cancers can now be classified by multidimensional criteria including tumour site, histology, primary - "driver" - molecular alterations, secondary molecular alterations, characteristics of the immune stroma, and genetic profile of the patient. The development of tools for the characterisation of the cancers, as well as novel molecular and immune therapeutics are evolving at an unprecedented pace. In 2012, a list of future challenges was identified at the occasion of the European Organisation for Research and Treatment of Cancer (EORTC) 50(th) anniversary. Three years after, it is interesting to look back at the questions addressed then and to assess the progress of these questions. We propose here a novel set questions which have emerged from the recent publications in this area. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer 06/2015; 102(6 Suppl 1):S22-6. DOI:10.1016/S0007-4551(15)31214-5 · 0.60 Impact Factor

Publication Stats

10k Citations
2,130.48 Total Impact Points


  • 2008-2015
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 2002-2015
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2013-2014
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
  • 2008-2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2011
    • University of Tours
      Tours, Centre, France
  • 2004-2011
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 2009
    • Leiden University
      Leyden, South Holland, Netherlands
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 2008-2009
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2007
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2006
    • CHU de Lyon - Hôpital de la Croix-Rousse
      Lyons, Rhône-Alpes, France
  • 2004-2005
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France