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Poster Display session 2

3433 - Tumor Microvessel Density for predicting Nintedanib activity: data from the randomized CHIVA trial (a GINECO study)


29 Sep 2019


Poster Display session 2


Maud Villemin


Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250


M. Villemin1, N. ELIE2, C. Blanc-Fournier3, G. DE RAUGLAUDRE4, N. Raban5, A. Chevalier6, G. Ferron7, M. Kaminsky-Forrett8, F. Beurrier9, S. Hamizi10, P. combe11, S. Abadie Lacourtoisie12, J. Meunier13, A. Floquet14, J. Alexandre15, L. Venat-Bouvet16, C. Louvet17, L. Favier18, I. Licaj19, J. Florence20

Author affiliations

  • 1 Inserm Unit U1086, Anticipe, Unité De Recherche Interdisciplinaire Pour La Prévention Et Le Traitement Des Cancers, Axe Bioticla (biologie Et Thérapies Innovantes Des Cancers De L’ovaire), Centre Francois Baclesse, 14076 - Caen/FR
  • 2 Structure Fédérative 4206 Icore Ufr Des Sciences - Département De Biologie Et Sciences De La Terre, Université Caen Normandie, CS 14032 - 14032 - CAEN cedex /FR
  • 3 Service De Pathologie, Centre Francois Baclesse, 14076 - CAEN Cedex/FR
  • 4 Oncologie Radiothérapie, Institut Sainte-Catherine, 84918 - Avignon/FR
  • 5 Pôle Régional De Cancérologie, Service D'oncologie, Hôpital de la Milétrie - CHU de Poitiers, 86021 - Poitiers Cédex/FR
  • 6 Cancerologie Gynecologie, Centre Oscar Lambret, 59020 - Lille/FR
  • 7 Département De Chirurgie Oncologique, Institut Claudius Regaud, 31059 - Toulouse Cédex/FR
  • 8 Oncologie Médicale, ICL Institut de Cancérologie de Lorraine, 54511 - Vandoeuvre-les-Nancy Cédex/FR
  • 9 Cancérologie Médicale - Gynécologie, Centre Léon Bérard, 69008 Lyon - Lyon/FR
  • 10 Oncologie Medicale, Centre Hospitalier Lyon Sud, 69495 - Pierre Bénite/FR
  • 11 Oncologie Medicale, Hopital European George Pompidou, 75015 - Paris/FR
  • 12 Oncologie Medicale Gynécologique, Centre Paul Papin, 49055 - Angers/FR
  • 13 Service D'oncologie Médicale, Centre Hospitalier Régional d'Orléans, 45067 - Orleans Cédex/FR
  • 14 Oncologie Médicale, Institute Bergonié, 33076 - Bordeaux/FR
  • 15 Unité D'oncologie Médicale, Hôpital Cochin, 75014 - PARIS Cédex/FR
  • 16 Oncologie Médicale, Centre Hospitalier Universitaire Dupuytren, 87042 - Limoges Cédex/FR
  • 17 Oncologie Médicale, Institut Mutualiste Montsouris, 75014 - Paris/FR
  • 18 Oncologie Médicale, Centre Georges François Leclerc, 21079 - Dijon Cédex/FR
  • 19 Clinical Research, Centre Francois Baclesse, 14076 - Caen/FR
  • 20 Calvados, Centre Francois Balesse, 14000 - CAEN/FR


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Abstract 3433


Tumour Microvessel density (MVD) is often used as a surrogate marker for tumoral angiogenic activity. In the randomized phase II neo-adjuvant CHIVA trial, ovarian cancer patients (pts) treated with standard chemotherapy plus Nintedanib (Ni) compared to chemotherapy alone had a reduced rate of complete surgical resection at interval debulking surgery (IDS), worse PFS and OS. To explain these results we assessed the predictive/prognostic value of MVD at baseline and the MVD decrease from baseline to IDS.


Paired tumours from baseline and IDS were available from 79/188 randomized pts. A total of 158 virtual slides of immunostained tumor section with anti-CD31 were analysed. MVD was quantified by an image processing on whole tumor section. MVD high level was defined as MVD > 33.5 vessel/mm² which is the highest Youden index on the ROC curve for PFS. The relationship between MVD at baseline and PFS and OS was evaluated using Kaplan-Meier survival estimates.


Main characteristics of the 79 pts were similar to the overall CHIVA population: mean age (62 years), ECOG performance status = 0 (34%), high-grade serous histology (75%). At baseline, MVD was similar in both arms and was low for 35% and 30% of the pts in the Ni and control arm respectively. The rate of complete resection (CC0) was 56% in the Ni arm versus 70% in the control arm.

In the low MVD group median PFS was 13.3 months (95%CI 11 – 22.2) versus 17 months (95%CI 13.7 – 20.5) in the high MVD group (p = 0.85). In the low MVD group, PFS in the Ni and control arm were 12.8 (95%CI 10.7-22.2) and 21.3 months (95%CI 12.5-NA) respectively (p = 0.08). The corresponding PFS in the high MVD group were 18.0 (95%CI 14.4-21.6) vs 14.5 months (95%CI 12.4-22.5) (p = 0.22). No difference was observed for OS. Baseline MVD was not associated with the rate of CC0. There was no significant difference in the decrease of MVD at IDS between the Ni arm (38% of the pts) and the control arm (48%, p = 0.4).


The negative impact of Nintedanib in patients with low baseline MVD tumours may be one explanation of the poor PFS rate observed in the Nintedanib arm of the CHIVA trial.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study



Health ministry grants( PHRC).


C. Blanc-Fournier: Honoraria (self): Roche. N. Raban: Travel / Accommodation / Expenses: Roche. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche. A. Floquet: Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. J. Alexandre: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self): PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen. C. Louvet: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca. J. Florence: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Travel / Accommodation / Expenses: Janssen. All other authors have declared no conflicts of interest.

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