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Poster Discussion – CNS tumours

3418 - GEINO 1402: A Phase Ib Dose-Escalation Study Followed by an Extension Phase to Evaluate Safety and Efficacy of Crizotinib in Combination with Temozolomide (TMZ) and Radiotherapy (RT) in Patients with Newly Diagnosed Glioblastoma (GB)


28 Sep 2019


Poster Discussion – CNS tumours


Maria Martinez Garcia


Annals of Oncology (2019) 30 (suppl_5): v143-v158. 10.1093/annonc/mdz243


M. Martinez Garcia1, M.J. Gil2, E. Pineda3, M.C. Martin Soberón4, C. Mesia Barroso5, P. Foro1, J. Capellades1, B. Sarmiento6, J. Bruna2, E. Verger3, A. Taus Garcia1, F. Alameda1, A. Hernandez Lain6, G. Velasco7, J.M. Sepulveda Sanchez6

Author affiliations

  • 1 Medical Oncology, Hospital del Mar, 08003 - Barcelona/ES
  • 2 Medical Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 3 Medical Oncology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 4 Medical Oncology Department, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 5 Medical Oncology, ICO - Institut Català d'Oncologia l'Hospitalet (Hospital Duran i Reynals), 08908 - Hospitalet de Llobregat/ES
  • 6 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 7 Neuroscience, Universidad Complutense de Madrid, 28040 - Madrid/ES


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Abstract 3418


MET signaling has a role in gliomagenesis and glioma stem cell maintenance and midkine (ALK ligand) promotes resistance of glioma cells to anticancer therapies. Crizotinib is an ALK and c-MET inhibitor with a preclinical rationale to be tested in newly diagnosed GB.


Elegible patients received crizotinib in addition to standard RT and TMZ and then adjuvant TMZ. Maintenance treatment with crizotinib beyond 6 TMZ cycles was allowed. The primary objective was safety evaluation. Secondary objectives included efficacy (progression free survival (PFS) and overall survival (OS)) and an exploratory biomarker analysis. PFS and OS were estimated with Kaplan–Meier method. The results of the dose-escalation cohort (DE) have been reported previously. 250 mg/d was the crizotinib dose selected for the expansion cohort (EC). We report here safety and efficacy for the whole cohort.


38 patients (pts) were enrolled, 37 evaluable for safety and 36 for efficacy (12 included in DE). Median age 52 years (33-76). 44%were male. Median KPS 90%, Barthel 100%. 44% were MGMT methylated and 3 pts had IDH1/2 mutation. Most common related adverse events (AE) (all grades) included: nausea (67.6%), asthenia (62.2%), transaminase elevation (40.5%), neutropenia (32.4%) thrombocytopenia (29.7%), diarrhea (29.7%), anorexia (29.7%), vomiting (27%) and constipation (24.3%). In the EC 8/25 pts (32%) presented grade ≥3 AEs (transaminase elevation, thrombocytopenia). 97.2% finished concomitant therapy. 94.4% initiated adjuvant treatment, 67.7% completed 6 TMZ cycles. 18 pts (50%) started maintenance therapy. 8 pts are still on treatment. At the time of this analysis 24 pts have progressed and 1 died without progression. Median follow up was 13.7 months (m), median PFS was 10.78m (95% CI, 7.61-13.94), with 6 month PFS and 12 month PFS of 71.6% and 40.2% respectively. Median OS was 31.4 m(95% CI, 12.64-50.10) with 12month OS of 78.9% and 24month OS of 56.6%.


In this phase Ib study addition of crizotinib to standard RT and TMZ was safe and resulted in highly promising efficacy for newly diagnosed GB, deserving further investigation.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study





M. Martinez Garcia: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ROCHE; Travel / Accommodation / Expenses: PFIZER. E. Pineda: Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Amgen. All other authors have declared no conflicts of interest.

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