Regorafenib in combination with first-line chemotherapy for metastatic esophagogastric cancer Journal Article


Authors: Moy, R. H.; Dos Santos Fernandes, G.; Jonsson, P.; Chou, J. F.; Basunia, A.; Ku, G. Y.; Chalasani, S. B.; Boyar, M. S.; Goldberg, Z.; Desai, A. M.; Gabler, A.; Berger, M. F.; Tang, L. H.; Hechtman, J. F.; Kelsen, D. P.; Schattner, M.; Ilson, D. H.; Solit, D. B.; Taylor, B. S.; Schultz, N.; Capanu, M.; Janjigian, Y. Y.
Article Title: Regorafenib in combination with first-line chemotherapy for metastatic esophagogastric cancer
Abstract: Background: Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first-line chemotherapy in metastatic esophagogastric cancer. Materials and Methods: Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14 days and regorafenib 160 mg daily on days 4 to 10 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. Results: Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single-center phase II study (NCT01913639). The most common grade 3–4 treatment-related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6-month PFS was 53% (95% confidence interval [CI], 38%–71%), the objective response rate was 54% (95% CI, 37%–70%), and the disease control rate was 77% (95% CI, 67%–94%). Next-generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum-based chemotherapy. Conclusion: Regorafenib (one week on–one week off schedule) is well tolerated in combination with first-line FOLFOX but does not improve 6-month PFS relative to historical control. Implications for Practice: Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first-line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD-1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible. © AlphaMed Press 2019
Keywords: adult; cancer chemotherapy; clinical article; controlled study; treatment response; aged; overall survival; fatigue; neutropenia; fluorouracil; diarrhea; drug dose reduction; drug efficacy; hypertension; follow up; genetic analysis; anorexia; biological marker; metastasis; progression free survival; computer assisted tomography; multiple cycle treatment; phase 2 clinical trial; anemia; leukopenia; mucosa inflammation; nausea; neuropathy; thrombocytopenia; vomiting; epidermal growth factor receptor 2; continuous infusion; angiogenesis; protein p53; irinotecan; stomach cancer; open study; targeted therapy; taxane derivative; disease control; trastuzumab; epidermal growth factor receptor 3; oxaliplatin; k ras protein; esophagus cancer; hand foot syndrome; folinate calcium; good clinical practice; hematemesis; hypertransaminasemia; esophagogastric cancer; cdkn2a gene; rb1 gene; ccne1 gene; high throughput sequencing; regorafenib; ramucirumab; ccnd1 gene; human; male; female; priority journal; article
Journal Title: The Oncologist
Volume: 25
Issue: 1
ISSN: 1083-7159
Publisher: AlphaMed Press  
Date Published: 2020-01-01
Start Page: e68
End Page: e74
Language: English
DOI: 10.1634/theoncologist.2019-0492
PUBMED: 31570517
PROVIDER: scopus
PMCID: PMC6964136
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Joanne Fu-Lou Chou
    197 Chou
  2. Michelle S Boyar
    4 Boyar
  3. David Solit
    544 Solit
  4. Geoffrey Yuyat Ku
    119 Ku
  5. Marinela Capanu
    256 Capanu
  6. Yelena Yuriy Janjigian
    189 Janjigian
  7. Laura Hong Tang
    353 Tang
  8. David H Ilson
    322 Ilson
  9. Michael Forman Berger
    497 Berger
  10. Mark Schattner
    114 Schattner
  11. David P Kelsen
    428 Kelsen
  12. Barry Stephen Taylor
    191 Taylor
  13. Nikolaus D Schultz
    259 Schultz
  14. Jaclyn Frances Hechtman
    162 Hechtman
  15. Avni Mukund Desai
    10 Desai
  16. Karl Philip Jonsson
    42 Jonsson
  17. Amelia R Gabler
    3 Gabler
  18. Ryan Hideki Moy
    1 Moy