Efficacy of combined VEGFR1-3, PDGFα/β, and FGFR1-3 blockade using nintedanib for esophagogastric cancer Journal Article
| Authors: | Won, E.; Basunia, A.; Chatila, W. K.; Hechtman, J. F.; Chou, J. F.; Ku, G. Y.; Chalasani, S. B.; Boyar, M. S.; Goldberg, Z.; Desai, A. M.; Tuvy, Y.; Berger, M. F.; Tang, L.; Kelsen, D. P.; Schattner, M.; Ilson, D. H.; Capanu, M.; Solit, D. B.; Schultz, N.; Janjigian, Y. Y. |
| Article Title: | Efficacy of combined VEGFR1-3, PDGFα/β, and FGFR1-3 blockade using nintedanib for esophagogastric cancer |
| Abstract: | Purpose: 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 and Methods: 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. Results: 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). Conclusions: 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. © 2019 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 25 |
| Issue: | 13 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-07-01 |
| Start Page: | 3811 |
| End Page: | 3817 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-18-3789 |
| PUBMED: | 30952642 |
| PROVIDER: | scopus |
| PMCID: | PMC6606369 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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