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
Notes: Source: Scopus
Citation Impact
MSK Authors
  1. Joanne Fu-Lou Chou
    197 Chou
  2. David Solit
    544 Solit
  3. Geoffrey Yuyat Ku
    119 Ku
  4. Marinela Capanu
    256 Capanu
  5. Yelena Yuriy Janjigian
    189 Janjigian
  6. Laura Hong Tang
    353 Tang
  7. David H Ilson
    322 Ilson
  8. Michael Forman Berger
    497 Berger
  9. Mark Schattner
    114 Schattner
  10. David P Kelsen
    428 Kelsen
  11. Nikolaus D Schultz
    259 Schultz
  12. Elizabeth Siryeon Won
    29 Won
  13. Jaclyn Frances Hechtman
    162 Hechtman
  14. Avni Mukund Desai
    10 Desai
  15. Yaelle Tuvy
    8 Tuvy
  16. Walid Khaled Chatila
    23 Chatila