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

ABSTRACT: BACKGROUND: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. METHODS:Patients with treatment-naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo-controlled, double-blind trial to receive first-line mFOLFOX6 with or without ziv-aflibercept (4 mg/kg) every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS). RESULTS:Sixty-four patients were randomized to receive mFOLFOX6 and ziv-aflibercept (43 patients) or mFOLFOX6 and a placebo (21 patients). There was no difference in the PFS, overall survival, or response rate. Patients treated with mFOLFOX6/ziv-aflibercept tended to be more likely to discontinue study treatment for reasons other than progressive disease (P = .06). The relative dose intensity of oxaliplatin and 5-fluorouracil was lower in the mFOLFOX6/ziv-aflibercept arm during the first 12 and 24 weeks of the trial. There were 2 treatment-related deaths due to cerebral hemorrhage and bowel perforation in the mFOLFOX6/ziv-aflibercept cohort. CONCLUSIONS:Ziv-aflibercept did not increase the anti-tumor activity of first-line mFOLFOX6 in metastatic esophagogastric cancer, potentially because of decreased dose intensity of FOLFOX. Further evaluation of ziv-aflibercept in unselected, chemotherapy-naive patients with metastatic esophagogastric adenocarcinoma is not warranted.

SUBMITTER: Cleary JM

PROVIDER: S-EPMC6763367 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Cleary James M JM Horick Nora K NK McCleary Nadine Jackson NJ Abrams Thomas A TA Yurgelun Matthew B MB Azzoli Christopher G CG Rubinson Douglas A DA Brooks Gabriel A GA Chan Jennifer A JA Blaszkowsky Lawrence S LS Clark Jeffrey W JW Goyal Lipika L Meyerhardt Jeffrey A JA Ng Kimmie K Schrag Deborah D Savarese Diane M F DMF Graham Christopher C Fitzpatrick Bridget B Gibb Kathryn A KA Boucher Yves Y Duda Dan G DG Jain Rakesh K RK Fuchs Charles S CS Enzinger Peter C PC

Cancer 20190326 13

<h4>Background</h4>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.<h4>Methods</h4>Patients with treatment-naive metastatic esophagogastric adenocarcinoma wer ...[more]

PMID: 30913304

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Project description:Background: The prognosis of patients with metastatic colorectal cancer (mCRC) is poor, especially after failure of initial systemic therapy. The VELOUR study showed modestly prolonged overall survival (OS) with ziv-aflibercept plus 5-fluorouracil, leucovorin, and irinotecan (zFOLFIRI) vs. placebo+FOLFIRI after progression on 5-fluoruracil, leucovorin, and oxaliplatin (FOLFOX) ± bevacizumab. The utility of zFOLFIRI after bevacizumab+FOLFIRI is unknown and not recommended in NCCN guidelines. We explored whether zFOLFIRI may be active beyond progression on bevacizumab+FOLFIRI. Methods: We undertook a retrospective analysis of patients treated in routine clinical practice. A chart review was conducted for a cohort (N = 19) of advanced cancer patients (18 mCRC) who received zFOLFIRI from 2014 to 2018 at Fox Chase Cancer Center (FCCC). Analysis included time on zFOLFIRI, PFS, OS, CEA trends and adverse events. A second mCRC cohort (N = 26) from the Flatiron Health EHR-derived database treated with zFOLFIRI after prior bevacizumab+FOLFOX and bevacizumab+FOLFIRI was analyzed for time-on-treatment and overall survival. Results: Median age of mCRC cohort at zFOLFIRI treatment was 54 (FCCC; N = 18) and 62 (Flatiron Health-cohort; N = 26). Of 18 FCCC mCRC patients, 1 patient had prior bevacizumab+FOLFOX and ramucirumab+irinotecan prior to zFOLFIRI for 8.5 months. Of 17 FCCC mCRC patients with prior bevacizumab+FOLFIRI who received zFOLFIRI, 13 had mutant-KRAS, 3 WT-KRAS, and one BRAF-V600E. The patient with BRAF-V600E mutation achieved stable disease on zFOLFIRI after multiple BRAF-targeted therapies. One patient (WT-KRAS mCRC) remained on zFOLFIRI for 14 months. Of 14 patients with mutated-KRAS, 8 remained on zFOLFIRI for >5 months including 3 for >15 months. The rate-of-change in CEA measures on zFOLFIRI was significantly different (p = 0.004) between rapid progressors and those with PFS>4 months. For mCRC patients treated with zFOLFIRI in the 3rd line or greater (N = 18), median PFS was 7.1 months (214 days) and median OS was 13.8 months (416 days). Median time-on-treatment with zFOLFIRI in the Flatiron Health cohort was 4.4 months, median OS was 7.8 months, and longest time-on-treatment with zFOLFIRI was 266 days. Conclusions: In these small real-world cohorts, clinical meaningful stable disease and overall survival on zFOLFIRI beyond progression on bevacizumab+FOLFIRI was observed in patients with mCRC. Further exploration of this approach is warranted.

Project description:BackgroundMyopic choroidal neovascularization (CNV) is the most common sight-threatening complication associated with high myopia. The present study evaluated the efficacy and safety of the intravitreal injection of ziv-aflibercept in patients with myopic CNV.MethodsThis prospective interventional study was conducted on 20 eyes of 20 patients with active myopic CNV. Twelve patients were 40 years or older. This study was performed in the Ophthalmology Department of Tanta University Eye Hospital, Tanta University, Egypt. Optical coherence tomography (OCT) was performed for all patients at baseline and monthly after injection during the 6-month follow up period. The main outcome measures were changes in BCVA and CMT. The exploratory outcome measures were CNV size, IOP and the number of injections needed in each age group during the study period.ResultsPatients with myopic CNV younger than 40 years needed fewer injections (2.00 ± 0.76) than patients older than 40 years (2.50 ± 1.00), with no statistical significance detected between the two groups (p-value 0.246). CNV was smaller in the younger age group (p-value 0.209), best corrected visual acuity (BCVA) improved significantly in the younger and older age groups (p-values 0.001 and 0.028, respectively), and central macular thickness (CMT) decreased significantly after 6 months, from 242.88 ± 23.83 μm to 191.13 ± 13.83 μm in the younger age group and from 251.33 ± 26.60 μm to 197.08 ± 17.64 μm in the older age group (p = 0.001). No significant correlation was found between the final BCVA and either the spherical equivalent or central macular thickness after 6 months, with p-values of 0.135 and 0.145, respectively. No significant changes in IOP were detected in either group after the intravitreal injection.ConclusionZiv-aflibercept is a highly effective and safe drug in cases of active myopic CNV; however, a larger number of patients and a longer follow-up period are needed to confirm our results. This study was retrospectively registered at clinicaltrials.gov (ID: NCT04290195) on 26-2-2020.

Dataset Information

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

Publications

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

Similar Datasets

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