Reference Detail

Ref Type

Journal Article

PMID

(25910950)

Authors

Lee EQ, Kaley TJ, Duda DG, Schiff D, Lassman AB, Wong ET, Mikkelsen T, Purow BW, Muzikansky A, Ancukiewicz M, Huse JT, Ramkissoon S, Drappatz J, Norden AD, Beroukhim R, Weiss SE, Alexander BM, McCluskey CS, Gerard M, Smith KH, Jain RK, Batchelor TT, Ligon KL, Wen PY

Title

A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	21	16	2015 Aug 15	3610-8	Clin Cancer Res

URL

Abstract Text

Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, noncomparative, phase II study of radiation (RT) and temozolomide with or without vandetanib in patients with newly diagnosed glioblastoma (GBM).We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to standard RT and temozolomide with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age ≥ 18 years, Karnofsky performance status (KPS) ≥ 60, and not on enzyme-inducing antiepileptics were eligible. Primary endpoint was median overall survival (OS) from the date of randomization. Secondary endpoints included median progression-free survival (PFS), 12-month PFS, and safety. Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis.The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 patients (36 in the RT/temozolomide arm and 70 in the vandetanib/RT/temozolomide arm). Median OS was 15.9 months [95% confidence interval (CI), 11.0-22.5 months] in the RT/temozolomide arm and 16.6 months (95% CI, 14.9-20.1 months) in the vandetanib/RT/temozolomide (log-rank P = 0.75).The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong OS compared with the parallel control arm, leading to early termination of the study.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PTEN negative	glioblastoma	no benefit	Temozolomide + Vandetanib	Phase II	Actionable	In a Phase II trial, Caprelsa (vandetinib), in combination with radiation therapy and Temodar (temozolomide), demonstrated no difference in PFS and OS when compared between glioblastoma patients negative for PTEN versus those positive for PTEN (PMID: 25910950).	25910950
IDH1 R132H	glioblastoma	sensitive	Temozolomide + Vandetanib	Phase II	Actionable	In a Phase II trial, Caprelsa (vandetanib), in combination with Temodar (temozolomide) and radiation therapy, demonstrated a significant increase in PFS and OS in glioblastoma patients harboring IDH1 R132H compared to glioblastoma patients without IDH1 R132H (PMID: 25910950).	25910950