title: Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes).
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.
  
  
  CONCLUSIONS
  Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. p.mathilde@free.fr.|Université Claude Bernard Lyon 1, Lyon, France. p.mathilde@free.fr.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Penel-Page
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. isabelle.ray-coquard@lyon.unicancer.fr.|Université Claude Bernard Lyon 1, Lyon, France. isabelle.ray-coquard@lyon.unicancer.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. julie.larcade@gmail.com.|Université Claude Bernard Lyon 1, Lyon, France. julie.larcade@gmail.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Larcade
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. magali.girodet@lyon.unicancer.fr.
authors.forename: Magali
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authors.lastname: Girodet
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. laure.bouclier@lyon.unicancer.fr.
authors.forename: Laure
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authors.lastname: Bouclier
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. muriel.rogasik@lyon.unicancer.fr.
authors.forename: Muriel
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authors.lastname: Rogasik
authors.affiliation: Hôpital Mère-enfant, 7 quai Moncousu, Nantes, France. nadege.corradini@chu-nantes.fr.
authors.forename: Nadège
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authors.lastname: Corradini
authors.affiliation: CHU Hautepierre, 1 avenue Molière, Strasbourg, France. natacha.entz-werle@chru-strasbourg.fr.
authors.forename: Natacha
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authors.lastname: Entz-Werle
authors.affiliation: Institut Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif, France. laurence.brugieres@igr.fr.
authors.forename: Laurence
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authors.lastname: Brugieres
authors.affiliation: Institut Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif, France. julien.domont@gustaveroussy.fr.
authors.forename: Julien
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authors.lastname: Domont
authors.affiliation: Centre Oscar Lambret, 3 rue Frédéric Combemale, Lille, France. c-lervat@o-lambret.fr.
authors.forename: Cyril
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authors.lastname: Lervat
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris, France. sophie.piperno-neumann@curie.fr.
authors.forename: Sophie
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authors.lastname: Piperno-Neumann
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris, France. helene.pacquement@curie.fr.
authors.forename: Helène
authors.initials: H
authors.lastname: Pacquement
authors.affiliation: Centre Jean Perrin, 58 Rue Montalembert, Clermont-Ferrand, France. jobay@chu-clermontferrand.fr.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.affiliation: CHU La Timone, 264 rue Saint-Pierre, Marseille, France. jcgentet@ap-hm.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.affiliation: Centre Antoine Lacassagne, 33 Avenue Valombrose, Nice, France. antoine.thyss@nice.unicancer.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Thyss
authors.affiliation: CHU Jean Minjoz, 2 Bd Fleming, Besançon, France. chaigneau.loic@orange.fr.
authors.forename: Loic
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authors.lastname: Chaigneau
authors.affiliation: CHU Bretonneau, 2 Bd Tonnellé, Tours, France. narciso@med.univ-tours.fr.
authors.forename: Bérangère
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authors.lastname: Narciso
authors.affiliation: CHU Raymond Poincaré, 104 Bd Raymond Poincaré, Garches, France. helene.cornille@rpc.aphp.fr.
authors.forename: Helène
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authors.lastname: Cornille
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. jean.yves-blay@lyon.unicancer.fr.|Université Claude Bernard Lyon 1, Lyon, France. jean.yves-blay@lyon.unicancer.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France. perrine.marec-berard@ihope.fr.|Université Claude Bernard Lyon 1, Lyon, France. perrine.marec-berard@ihope.fr.
authors.forename: Perrine
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authors.lastname: Marec-Bérard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D056687:Off-Label Use; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012042:Registries; D019233:Retreatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents