ArticleCancers2022
Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Receptor tyrosine kinase targeted therapies in glioblastoma: a systematic review.Frontiers in medicine · 2026Pooled it
- Vebreltinib for Previously Treated Astrocytoma,Cancer communications (London, England) · 2026Trial
- Substituent Effects of Heptamethine Cyanine Dyes on Drug Uptake in Patient-Derived Glioma Cells.ChemMedChem · 2026Article
- Targeting MET and mTOR Synergistically Overcomes Adaptive Resistance in Glioblastoma.International journal of molecular sciences · 2026Article
- Midkine and pleiotrophin in glioma: From mechanistic insights to therapeutic potential.Neoplasia (New York, N.Y.) · 2026Review
- Efficacy of tepotinib in patients with high-grade glioma withNeuro-oncology practice · 2026Article
- Review
- Targeted immunotherapies for anaplastic lymphoma kinase-positive pediatric tumors: current advances and future perspectives.Frontiers in immunology · 2026Review
- BNIP3-mTOR Signaling Mediates Resistance to MET Inhibition in Glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Coordinated changes in midkine expression and midkine-associated multiomic profile in glioma microenvironment.Scientific reports · 2025Article
- Treatment of a newly diagnosed glioblastoma harboring MET amplification with vebreltinib in combination with radiotherapy: a case report.Discover oncology · 2025Article
- Targeting the MDK/c-Myc complex to overcome temozolomide resistance in glioma.Clinical and translational medicine · 2025Article
- Review
- Prolonged complete response to adjuvant tepotinib in a patient with newly diagnosed disseminated glioblastoma harboring mesenchymal-epithelial transition fusion.The oncologist · 2025Article
- Article
- Current status of precision oncology in adult glioblastoma.Molecular oncology · 2024Review
- Evolution of Molecular Biomarkers and Precision Molecular Therapeutic Strategies in Glioblastoma.Cancers · 2024Review
- AberrantCells · 2024Review
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- Cyanine Dye Conjugation Enhances Crizotinib Localization to Intracranial Tumors, Attenuating NF-κB-Inducing Kinase Activity and Glioma Progression.Molecular pharmaceutics · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundMET-signaling and midkine (ALK ligand) promote glioma cell maintenance and resistance against anticancer therapies. ALK and c-MET inhibition with crizotinib have a preclinical therapeutic rationale to be tested in newly diagnosed GBM.
methodsEligible patients received crizotinib with standard radiotherapy (RT)/temozolomide (TMZ) followed by maintenance with crizotinib. The primary objective was to determine the recommended phase 2 dose (RP2D) in a 3 + 3 dose escalation (DE) strategy and safety evaluation in the expansion cohort (EC). Secondary objectives included progression-free (PFS) and overall survival (OS) and exploratory biomarker analysis.
resultsThe study enrolled 38 patients. The median age was 52 years (33-76), 44% were male, 44% were MGMT methylated, and three patients had IDH1/2 mutation. In DE, DLTs were reported in 1/6 in the second cohort (250 mg/QD), declaring 250 mg/QD of crizotinib as the RP2D for the EC. In the EC, 9/25 patients (32%) presented grade ≥3 adverse events. The median follow up was 18.7 months (m) and the median PFS was 10.7 m (95% CI, 7.7-13.8), with a 6 m PFS and 12 m PFS of 71.5% and 38.8%, respectively. At the time of this analysis, 1 died without progression and 24 had progressed. The median OS was 22.6 m (95% CI, 14.1-31.1) with a 24 m OS of 44.5%. Molecular biomarkers showed no correlation with efficacy.
conclusionsThe addition of crizotinib to standard RT and TMZ for newly diagnosed GBM was safe and the efficacy was encouraging, warranting prospective validation in an adequately powered, randomized controlled study.
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