FOLFOX plus ziv‐aflibercept or placebo in first‐line metastatic esophagogastric adenocarcinoma: A double‐blind, randomized, multicenter phase 2 trial

Antiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv‐aflibercept, could improve the efficacy of first‐line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5‐ fluorouracil) in metastatic esophagogastric adenocarcinoma.

[1]  C. Hsueh,et al.  Targeted and novel therapy in advanced gastric cancer , 2019, Experimental Hematology & Oncology.

[2]  Mei-ling Zhu,et al.  Prognostic value and association of Lauren classification with VEGF and VEGFR-2 expression in gastric cancer , 2019, Oncology letters.

[3]  J. Lacy,et al.  RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. , 2018 .

[4]  J. Meyerhardt,et al.  Patterns of chemotherapy (CT) use in a U.S.-wide cohort of patients (pts) with metastatic gastric cancer (MGC). , 2018 .

[5]  P. Philip,et al.  Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  Quan P. Ly,et al.  Gastric Cancer, Version 3.2016; Clinical Practice Guidelines in Oncology , 2016 .

[7]  A. Benson,et al.  CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Ying Cheng,et al.  Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J. Roh,et al.  Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  R. Kelly,et al.  State of the art management of metastatic gastroesophageal cancer. , 2015, Annals of translational medicine.

[11]  R. Jain,et al.  Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. , 2014, Cancer cell.

[12]  Naotoshi Sugimoto,et al.  Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. , 2014, The Lancet. Oncology.

[13]  K. Kelly,et al.  Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Jianming Xu,et al.  Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study) , 2014, Gastric Cancer.

[15]  J. Berlin,et al.  Aflibercept—a Decoy VEGF Receptor , 2014, Current Oncology Reports.

[16]  C. Fuchs,et al.  Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial , 2014, The Lancet.

[17]  J. Neal,et al.  A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer , 2013, British Journal of Cancer.

[18]  Thierry Gil,et al.  Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. , 2013, The Lancet. Oncology.

[19]  E. Van Cutsem,et al.  Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  M. Shah,et al.  Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  S. Loibl,et al.  Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis , 2011, BMC Cancer.