Michael Stahl1, Annett Maderer2, Florian Lordick3, Andre L Mihaljevic4, Stefan Kanzler5, Thomas Hoehler6, Peter Thuss-Patience7, Stefan Mönig8, Volker Kunzmann9, Sebastian Schroll10, Andreas Sandermann11, Andrea Tannapfel12, Hans-Joachim Meyer13, Christoph Schuhmacher4, Hansjochen Wilke1, Markus Moehler14. 1. Department of Medical Oncology, Kliniken Essen-Mitte, Essen, Germany. 2. Department of Internal Medicine II, University Clinic, Mainz, Germany. 3. University Cancer Center Leipzig (UCCL), University Medicine, Leipzig, Germany. 4. Department of Surgery, Klinikum rechts der Isar, Technische Universität, Munich, Germany. 5. Department of Internal Medicine II, Leopoldina Krankenhaus, Schweinfurt, Germany. 6. Department of Medicine I, Prosper Hospital, Recklinghausen, Germany. 7. Department of Hematology, Oncology and Tumor Immunology, Charite Universitätsmedizin Berlin, Berlin, Germany. 8. Service de chirurgie viscérale, Hôpitaux Universitaires Genève, Geneve, Switzerland. 9. Department of Medical Oncology, University Clinic, Würzburg, Germany. 10. Department of Hematology and Oncology, Klinikum Braunschweig, Germany. 11. Biostatistics, Wissenschaftlicher Service Pharma GmbH, Langenfeld, Germany. 12. Institute of Pathology, Ruhr-University, Bochum, Germany. 13. German Society of Surgery, Berlin, Germany. 14. Department of Internal Medicine II, University Clinic, Mainz, Germany. Electronic address: markus.moehler@unimedizin-mainz.de.
Abstract
BACKGROUND:Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed. PATIENTS AND METHODS: To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab. The primary end-point was the histological response rate after neoadjuvant therapy. The expression status and gene copy number of EGFR, HER2, and MET were determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Plasma samples were collected before the first cycle of neoadjuvant chemotherapy. RESULTS: Overall, 160 patients (80 versus 80) were eligible. The majority (82% versus 80%) showed lymph node involvement. Rate of R0-resection, percentage of patients with downstaging to ypT0-2 at pathohistological evaluation, and rate of major histological response was equal in both arms. Toxicity was increased by panitumumab with regard to thromboembolic events and skin toxicity. Patients with tumour EGFR, HER2 or MET expression had shorter progression-free and overall survival. FISH positivity for these markers was associated with shorter survival independent of therapy. High levels of soluble EGFR in particular predicted poor survival in the panitumumab arm. CONCLUSION: The addition of panitumumab to ECX did not improve downstaging of locally advanced EGC. Low plasma levels of pathway-associated proteins such as sEGFR may identify a group of patients that benefit from EGFR-directed therapy. CLINICALTRIALS.GOV: NCT01234324.
RCT Entities:
BACKGROUND: Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed. PATIENTS AND METHODS: To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab. The primary end-point was the histological response rate after neoadjuvant therapy. The expression status and gene copy number of EGFR, HER2, and MET were determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Plasma samples were collected before the first cycle of neoadjuvant chemotherapy. RESULTS: Overall, 160 patients (80 versus 80) were eligible. The majority (82% versus 80%) showed lymph node involvement. Rate of R0-resection, percentage of patients with downstaging to ypT0-2 at pathohistological evaluation, and rate of major histological response was equal in both arms. Toxicity was increased by panitumumab with regard to thromboembolic events and skin toxicity. Patients with tumourEGFR, HER2 or MET expression had shorter progression-free and overall survival. FISH positivity for these markers was associated with shorter survival independent of therapy. High levels of soluble EGFR in particular predicted poor survival in the panitumumab arm. CONCLUSION: The addition of panitumumab to ECX did not improve downstaging of locally advanced EGC. Low plasma levels of pathway-associated proteins such as sEGFR may identify a group of patients that benefit from EGFR-directed therapy. CLINICALTRIALS.GOV: NCT01234324.
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