B Schultheis1, D Reuter2, M P Ebert3, J Siveke3, A Kerkhoff4, W E Berdel4, R Hofheinz5, D M Behringer6, W E Schmidt7, E Goker8, S De Dosso9, M Kneba10, S Yalcin11, F Overkamp12, F Schlegel13, M Dommach14, R Rohrberg15, T Steinmetz16, M Bulitta17, D Strumberg18. 1. Department of Hematology/Oncology, University Bochum, Marien Hospital Herne, Herne;. Electronic address: beate.schultheis@elisabethgruppe.de. 2. Oncoscience AG, Wedel (recently Schenefeld). 3. Klinikum Rechts der Isar TU München, München. 4. University Hospital Münster, Münster. 5. Department of Hematology and Medical Oncology, University Medical Center Mannheim, Mannheim. 6. Augusta-Kranken-Anstalt, Bochum. 7. St. Josef Hospital, Med. Klinik I, Bochum, Germany. 8. Ege University Medical School, Izmir, Turkey. 9. Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. 10. Department of Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany. 11. Hacettepe University Hospital, Ankara, Turkey. 12. Medical Practice for Oncology and Hematology, Recklinghausen. 13. St. Antonius Hospital, Eschweiler. 14. Sana-Kliniken, Medizinisches Versorgungszentrum Onkologie, Düsseldorf. 15. Gemeinschaftspraxis und Tagesklinik fuer Haematologie, Onkologie und Gastroenterologie, Halle. 16. Group Practice Hematology/Oncology Cologne, Cologne. 17. CRM Biometrics GmbH, Rheinbach, Germany. 18. Department of Hematology/Oncology, University Bochum, Marien Hospital Herne, Herne.
Abstract
BACKGROUND: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. RESULTS: A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). CONCLUSION: This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.
BACKGROUND: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. RESULTS: A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). CONCLUSION: This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.
Authors: Christopher Gromisch; Motaz Qadan; Mariana Albuquerque Machado; Kebin Liu; Yolonda Colson; Mark W Grinstaff Journal: Cancer Res Date: 2020-03-27 Impact factor: 12.701
Authors: Annika L Windon; Arturo Loaiza-Bonilla; Christopher E Jensen; Michael Randall; Jennifer J D Morrissette; Stuti G Shroff Journal: J Gastrointest Oncol Date: 2018-02