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Poster Discussion – Sarcoma

1399 - Phase 1 combination dose-finding/phase 2 expansion cohorts of lenvatinib + etoposide + ifosfamide in patients (pts) aged 2 to _25 years with relapsed/refractory (r/r) osteosarcoma


28 Sep 2019


Poster Discussion – Sarcoma


Nathalie Gaspar


Annals of Oncology (2019) 30 (suppl_5): v683-v709. 10.1093/annonc/mdz283


N. Gaspar1, F.J. Bautista Sirvent2, R. Venkatramani3, A. Longhi4, C. Lervat5, M. Casanova6, I. Aerts7, S.S. Bielack8, N. Entz-Werle9, S. Strauss10, C. He11, E. Thebaud12, F. Locatelli13, B. Morland14, S. Gallego Melcon15, A. Cañete Nieto16, P. Marec- Bérard17, M. Gambart18, C. Rossig19, Q. Campbell-Hewson20

Author affiliations

  • 1 Department Of Oncology For Child And Adolescent, Gustave Roussy Cancer Campus, 94800f - Villejuif/FR
  • 2 Pediatric Oncology, Hospital Infantil Universitario Niño Jesús, 28009 - Madrid/ES
  • 3 Pediatrics, Texas Children’s Hospital, 77030 - Houston/US
  • 4 Musculoskeletal Oncology, Istituto Ortopedico Rizzoli, 40136 - Bologna/IT
  • 5 Pediatrics, Centre Oscar Lambret Lille, 59000 - Lille/FR
  • 6 Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 7 Pediatrics, Institut Curie, PSL Research University, Oncology Center SIREDO, Paris/FR
  • 8 Pediatric Oncology, Klinikum Stuttgart - Olgahospital, 70174 - Stuttgart/DE
  • 9 Onco-hematological Pediatrics, Chu Strasbourg - Hopital Hautepierre, 67200 - Strasbourg/FR
  • 10 Department Of Oncology, University College London Hospital, NW1 2BU - London/GB
  • 11 Biostatistics, Eisai Inc., 07677 - Woodcliff/US
  • 12 Oncology And Haematology, CHU Nantes - Hôpital Mère-Enfant, 44093 - Nantes/FR
  • 13 Pediatric Hematology-oncology, Ospedale Pediatrico Bambino Gesù, Roma, 00165 - University of Pavia/IT
  • 14 Oncology And Haematology, Birmingham Children's Hospital, B4 6NH - Birmingham/GB
  • 15 Oncology And Haematology, University Hospital Vall d’Hebron, Barcelona/ES
  • 16 Pediatric Oncology, Hospital Universitario y Politecnico La Fe Hospital La Fe, 46026 - Valencia/ES
  • 17 Pediatric Oncology, Centre Léon Bérard, Lyon/FR
  • 18 Oncology And Haematology, CHU de Toulouse - Hôpital des Enfants, 31300 - Toulouse/FR
  • 19 Pediatric Hematology And Oncology, University Children’s Hospital Muenster, Pediatric Hematology and Oncology, 48149 - Muenster/DE
  • 20 Pediatric Oncology, The Great North Children’s Hospital, Royal Victoria Infirmary, NE14LP - Newcastle Upon Tyne/GB


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Abstract 1399


Lenvatinib (LEN) is a multikinase inhibitor of VEGFR1–3 and other targets. We report data from phase Ib dose-finding and phase II expansion cohorts of LEN + etoposide + ifosfamide in pts with r/r osteosarcoma.


Pts were aged 2 to ≤ 25 years with r/r osteosarcoma and <2 prior VEGF-targeted therapies. The phase Ib starting dose was LEN 11 mg/m2/day + ifosfamide 3000 mg/m2 + etoposide 100 mg/m2 daily/3 days. On determination of the recommended phase II dose (RPh2D) of LEN + chemo, pts were enrolled into the phase II expansion cohort. Primary end points: phase Ib, RPh2D; phase II, 4 months’ progression-free survival (PFS-4).


In the phase Ib dose-finding cohort (n = 22), pts received LEN 11 mg/m2 (n = 7) and 14 mg/m2 (n = 15) + chemo. Dose-limiting toxicities were: Grade (G) 4 thrombocytopenia (n = 1; LEN 11 mg/m2), G4 thrombocytopenia and G3 epistaxis (n = 1; LEN 14 mg/m2), G2 oral dysesthesia, G3 muscle spasm, and G2 back pain (n = 1; LEN 14 mg/m2). RPh2D was LEN 14 mg/m2 + chemo. In the expansion cohort (n = 20), the median number of LEN cycles received was 4 (range: 1–7). As reported in the database, the most frequent treatment-emergent adverse events (TEAEs) were platelet count decreased/thrombocytopenia (50%/30%), neutropenia/neutrophil count decreased (45%/25%), anemia (45%), nausea (40%), ALT increased, diarrhea, and white blood cell count decreased (30% each). Most frequent G ≥ 3 TEAEs were neutropenia/neutrophil count decreased (45%/25%), platelet count decreased/thrombocytopenia (40%/20%), white blood cell count decreased (30%), and anemia (25%). Pneumothorax was observed in the dose-finding cohort (n = 6) and expansion cohort (n = 1); 2 (dose-finding cohort) were ≥G3; and 1 was post-thoracotomy. 4 Pts (dose-finding cohort) discontinued treatment due to TEAEs. There were no treatment-related fatal serious AEs. In the dose-finding combination cohort, 12/18 evaluable pts (66.7%) achieved PFS-4. In the phase II expansion cohort, 5/8 evaluable pts (62.5%) achieved PFS-4.


The combination of RPh2D LEN (14 mg/m2) + chemo had a manageable safety profile with promising preliminary evidence of efficacy.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Eisai Inc.


Eisai Inc.


A. Longhi: Non-remunerated activity/ies, non-financial support: PharmaMar, Takeda; Research grant / Funding (institution): Takeda. M. Casanova: Advisory / Consultancy, advisory role: Bayer; Advisory / Consultancy, advisory role: Lilly; Advisory / Consultancy, advisory role: Roche; Advisory / Consultancy, advisory role: Tesaro. S.S. Bielack: Travel / Accommodation / Expenses, site fees for study preparation: Eisai; Travel / Accommodation / Expenses, personal fees from Clinigen: Clinigen; Travel / Accommodation / Expenses, personal fees from Lilly: Lilly; Travel / Accommodation / Expenses, personal fees from Novartis: Novartis; Travel / Accommodation / Expenses, personal fees from Bayer: Bayer; Travel / Accommodation / Expenses, personal fees from Pfizer: Pfizer; Travel / Accommodation / Expenses, personal fees from Isofol: Isofol; Travel / Accommodation / Expenses, personal fees from Sensorion: Sensorion; Travel / Accommodation / Expenses, personal fees from Ipsen: Ipsen; Advisory / Consultancy, Institution negotiating consultancy agreement with Eisai: Eisai. S. Gallego Melcon: Travel / Accommodation / Expenses: Loxo Oncology; Advisory / Consultancy: Bayer, Eusa. All other authors have declared no conflicts of interest.

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