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Ref Type Journal Article
PMID (30952642)
Authors Won E, Basunia A, Chatila WK, Hechtman JF, Chou JF, Ku GY, Chalasani SB, Boyar MS, Goldberg Z, Desai AM, Tuvy Y, Berger MF, Tang L, Kelsen DP, Schattner M, Ilson DH, Capanu M, Solit DB, Schultz N, Janjigian YY
Title Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 25
Issue 13
Date 2019 Jul 01
URL
Abstract Text VEGFR2-directed therapy is commonly used to treat metastatic esophagogastric cancer, but disease progresses in most patients within months. Therapeutic resistance is likely mediated in part by co-occurring amplifications of the genes for multiple oncogenic receptor tyrosine kinases (RTK). We therefore tested the efficacy of combined inhibition of VEGFR1-3, PDGFα/β, and FGFR1-3 using nintedanib.Patients with metastatic esophagogastric adenocarcinoma and disease progression on first-line chemotherapy were treated with nintedanib 200 mg twice daily. The primary endpoint was progression-free survival (PFS) at 6 months; secondary endpoints included tumor response and safety. Tumor biopsies were profiled by targeted capture next-generation sequencing (NGS) to identify molecular predictors of drug response.The study achieved its primary endpoint; 6 of 32 patients (19%) were progression-free at 6 months. With a median follow-up of 14.5 months among survivors, median overall survival (OS) was 14.2 months [95% confidence interval (CI), 10.8 months-NR]. Nintedanib was well tolerated; grade ≥ 3 toxicities were uncommon and included grade 3 hypertension (15%) and liver enzyme elevation (4%). FGFR2 alterations were identified in 18% of patients but were not predictive of clinical outcome on nintedanib therapy. Alterations in cell-cycle pathway genes were associated with worse median PFS (1.61 months for patients with cell-cycle pathway alterations vs. 2.66 months for patients without, P = 0.019).Nintedanib treatment resulted in modest disease stabilization in patients with metastatic esophagogastric cancer. Alterations in cell-cycle pathway genes and increased global copy-number alteration (CNA) burden warrant further study as prognostic or predictive biomarkers.

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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
Unknown unknown gastroesophageal junction adenocarcinoma not applicable Nintedanib Phase II Actionable In a Phase II trial, Ofev (nintedanib) was well tolerated and the study met its primary endpoint, resulted in progression-free survival at 6-months in 19% (6/32) of patients with esophageal/GEJ (n=17) or gastric (n=15) adenocarcinoma, with a median follow-up of 14.5 months and a median overall survival of 14.2 months (PMID: 30952642; NCT02234596). 30952642
Unknown unknown esophagus adenocarcinoma not applicable Nintedanib Phase II Actionable In a Phase II trial, Ofev (nintedanib) was well tolerated and the study met its primary endpoint, resulted in progression-free survival at 6-months in 19% (6/32) of patients with esophageal/GEJ (n=17) or gastric (n=15) adenocarcinoma, with a median follow-up of 14.5 months and a median overall survival of 14.2 months (PMID: 30952642; NCT02234596). 30952642
Unknown unknown gastric adenocarcinoma not applicable Nintedanib Phase II Actionable In a Phase II trial, Ofev (nintedanib) was well tolerated and the study met its primary endpoint, resulted in progression-free survival at 6-months in 19% (6/32) of patients with esophageal/GEJ (n=17) or gastric (n=15) adenocarcinoma, with a median follow-up of 14.5 months and a median overall survival of 14.2 months (PMID: 30952642; NCT02234596). 30952642