Publications by authors named "Tiana Raveloarivahy"

6 Publications

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A phase II study of monalizumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: The I1 cohort of the EORTC-HNCG-1559 UPSTREAM trial.

Eur J Cancer 2021 Oct 9;158:17-26. Epub 2021 Oct 9.

Service d'Oncologie Médicale, Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium. Electronic address:

Purpose: Monalizumab is a monoclonal antibody targeting the inhibitory natural killer group 2A (NKG2A) receptor localised on natural killer (NK) and T cells. Its ligand, the human leukocyte antigen E (HLA-E), is overexpressed in squamous cell carcinoma of the head and neck (SCCHN). By targeting the HLA-E-NKG2A pathway, monalizumab may enhance NK and T cell activity.

Experimental Design: The UPSTREAM trial is a biomarker-driven umbrella trial studying targeted therapies and immunotherapies in patients with recurrent/metastatic (R/M) SCCHN progressing after platinum therapy. The immunotherapy 1 (I1) cohort was a phase II, single-arm substudy evaluating monalizumab (10 mg/kg intravenously on day 1 of a 14-day cycle). The primary end-point was the objective response (OR) rate (Response Evaluation Criteria in Solid Tumours 1.1) over the first 16 weeks. A two-stage Simon design was used (H1 15%, H0 3%, α 8%, power 90%) with pre-planned interruption of accrual if no OR was observed after the first 25 patients.

Results: Twenty-six eligible patients were enrolled. Seventeen (65%) patients had received ≥2 previous lines of systemic treatment, and 15 (58%) patients were PD(-L)1 inhibitor pretreated. No OR was observed. Stable disease was observed in 6 patients (23%) with a median duration of 3.8 months (95% confidence interval [CI]: 2.7-NE). The median progression-free survival and overall survival were 1.7 months (95% CI: 1.5-1.8) and 6.7 months (95% CI: 3.0-9.6), respectively. The most frequent treatment-related adverse event was grade I/II fatigue (19%).

Conclusions: Monalizumab monotherapy has limited activity in R/M SCCHN. The I1 cohort did not meet its primary objective. Monalizumab combined with durvalumab is under investigation within UPSTREAM.
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http://dx.doi.org/10.1016/j.ejca.2021.09.003DOI Listing
October 2021

A multinational, multi-tumour basket study in very rare cancer types: The European Organization for Research and Treatment of Cancer phase II 90101 'CREATE' trial.

Eur J Cancer 2019 03 14;109:192-195. Epub 2019 Jan 14.

Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/j.ejca.2018.12.013DOI Listing
March 2019

Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial.

Blood 2018 03 1;131(13):1456-1463. Epub 2018 Feb 1.

Lymphoma Study Association Imaging, Hôpital Henri Mondor, Créteil, France; and.

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS ( < .0001) and OS ( = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well.
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http://dx.doi.org/10.1182/blood-2017-07-795476DOI Listing
March 2018

Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial.

Eur J Cancer 2017 12 14;87:147-163. Epub 2017 Nov 14.

Gustave Roussy, Department of Medical Oncology, Villejuif, France.

Purpose: Papillary renal-cell carcinoma type 1 (PRCC1) is associated with MET gene alterations. Our phase II trial prospectively assessed the efficacy and safety of crizotinib in patients with advanced/metastatic PRCC1 with or without MET mutations (MET+ and MET-).

Experimental Design: Eligible patients with reference pathology-confirmed PRCC1 received 250 mg oral crizotinib twice daily. Patients were attributed to MET+/MET- sub-cohorts by the sequencing of exons 16-19 of the MET gene in tumour tissue. The primary end-point was objective response rate (ORR). If at least two of the first 12 eligible and evaluable MET+ patients achieved a confirmed partial response (PR) or complete response (CR) (in accordance with the Response Evaluation Criteria in Solid Tumours, version 1.1), a maximum of 35 patients were enrolled. Secondary end-points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), PFS rate (PFSR), overall survival (OS) and safety.

Results: Forty-one patients provided consent, of whom 23 were eligible, treated and evaluable. In four MET+ patients, two achieved PR and one had stable disease (SD) (ORR 50%; 95% confidence interval [CI]: 6.8-93.2), DOR was 21.8 and 37.3 months, 1-year PFSR: 75.0% (95% CI: 12.8-96.1) and 1-year OS: 75.0% (95% CI: 12.8-96.1). Among 16 MET- patients, one achieved a PR lasting more than 9.9 months and 11 had SD (ORR: 6.3%; 95% CI: 0.2-30.2), 1-year PFSR: 27.3% (95% CI: 8.5-50.4) and 1-year OS: 71.8% (95% CI: 41.1-88.4). Among three patients with unknown MET status (MET?) due to technical failure, one achieved PR lasting more than 6.9 months, and one had SD (ORR 33.3%, 95% CI: 0.8-90.6), 1-year PFSR: 66.7% (95% CI: 5.4-94.5) and 1-year OS: 100%. MET amplification was found post hoc in one MET+ patient (PR, DOR: 37.3 months), and one MET- case who had SD. Common treatment-related adverse events were oedema (47.8%), fatigue (47.8%), nausea (39.1%), diarrhoea (39.1%) and blurred vision (34.8%).

Conclusion: Crizotinib is active and well tolerated in advanced, metastatic PRCC1, achieving objective responses and long-lasting disease control in patients with MET mutations or amplification. Sporadic, durable responses are also seen in MET- and MET? cases, suggesting the presence of other alterations of MET or alternative pathways.
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http://dx.doi.org/10.1016/j.ejca.2017.10.014DOI Listing
December 2017

Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial.

J Clin Oncol 2017 Jun 14;35(16):1786-1794. Epub 2017 Mar 14.

Marc P.E. André, Université Catholique de Louvain, Yvoir; Catherine Fortpied, Valeria Fiaccadori, and Tiana Raveloarivahy, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Théodore Girinsky and Christophe Fermé, Institut Gustave Roussy, Villejuif; Oumédaly Reman, Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire, Caen; Pauline Brice, Assistance Publique des Hopitaux de Paris Hôpital Saint-Louis; Richard Delarue, Assistance Publique des Hopitaux de Paris Hôpital Universitaire Necker-Enfants Maladies, Paris; Olivier Casasnovas, Centre Hospitalier Universitaire le Bocage and Institut National de la Santé et de la Recherche Médicale, Dijon; Véronique Edeline, Hôpital René Hugenin-Institut Curie, Saint Cloud; Réda Bouabdallah, Institut Paoli Calmette, Marseille; Catherine Sebban, Hematology Centre Léon Bérard, Lyon; Aspasia Stamatoullas, Centre Henri Becquerel, Rouen; Michel Meignan, Henri Mondor University Hospitals, Créteil, France; Massimo Federico and Monica Bellei, University of Modena and Reggio Emilia, Modena; Manuel Gotti, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia; Alessandro Re, Spedali Civili Hospital, Brescia; Francesco Merli and Annibale Versari, Arcispedale Santa Maria Nuova Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy; Richard van der Maazen and John Raemaekers, Radboud University Medical Center, Nijmegen; Gustaaf van Imhoff, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands; and Lena Specht and Martin Hutchings, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated-according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)-stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET-361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.
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http://dx.doi.org/10.1200/JCO.2016.68.6394DOI Listing
June 2017

Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial.

J Clin Oncol 2014 Apr 17;32(12):1188-94. Epub 2014 Mar 17.

John M.M. Raemaekers and Richard van der Maazen, Radboud University Medical Center, Nijmegen; Pieternella J. Lugtenburg, Erasmus University Medical Center, Rotterdam; Gustaaf van Imhoff, University Medical Centre Groningen, Groningen, the Netherlands; Marc P.E. André and Thierry van der Borght, Centre Hospitalier Universitaire (CHU) L'Université Catholique de Louvain Mont Godinne, Yvoir; Yolande Lievens, Ghent University Hospital, Ghent; Tiana Raveloarivahy and Catherine Fortpied, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Massimo Federico and Monica Bellei, University of Modena and Reggio Emilia, Modena; Ercole Brusamolino, Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan; Manuel Gotti, Fondazione IRCCS Policlinico San Matteo, Pavia; Allessandro Re, Spedali Civili Hospital, Brescia; Elisabetta Abruzzese, San Eugenio Hospital, Tor Vergata University, Rome; Annibale Versari, Arcispedale Santa Maria Nuova, IRCCS di Reggio Emilia, Reggio Emilia, Italy; Theodore Girinsky and Christophe Fermé, Institut Gustave Roussy, Villejuif; Reman Oumedaly, CHU Caen; Stephane Bardet, Centre Francois Baclesse, Caen; Pauline Brice, Hôpital Saint-Louis, Paris; Reda Bouabdallah, Institut Paoli Calmette, Marseille; Catherine J. Sebban, Centre Léon Bérard, Lyon; Aspasia Stamatoullas, Centre Henri Becquerel, Rouen; Frank Morschhauser, CHU de Lille, Lille; Pierre Olivier, CHU Nancy, Nancy; Rene-Olivier Casasnovas, CHU de Dijon, Dijon; Michel Meignan, Hôpital Henri Mondor, Creteil, France; and Martin Hutchings, Rigshospitalet, Kopenhagen, Denmark.

Purpose: Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment.

Patients And Methods: Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted.

Results: The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET-negative patients.

Conclusion: On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.
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http://dx.doi.org/10.1200/JCO.2013.51.9298DOI Listing
April 2014
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