CONKO-006: A randomised double-blinded phase IIb-study of additive therapy with gemcitabine + sorafenib/placebo in patients with R1 resection of pancreatic cancer – Final results
Autor: | Hanno Riess, F. Lammert, U. Lindig, R.D. Hofheinz, Helmut Oettle, Sven Bischoff, C. Denzlinger, M Bahra, Axel Hinke, Uwe Pelzer, Jana K. Striefler, Michael Ghadimi, P. Stübs, Klaus Gellert, Georg Maschmeyer, Marianne Sinn, Torsten Liersch, D Waldschmidt, Michael Bitzer, Wolf O. Bechstein |
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Rok vydání: | 2020 |
Předmět: |
Adult
Male 0301 basic medicine Sorafenib Cancer Research medicine.medical_specialty Time Factors medicine.medical_treatment Adenocarcinoma Neutropenia Placebo Deoxycytidine Gastroenterology Drug Administration Schedule 03 medical and health sciences Pancreatectomy 0302 clinical medicine Double-Blind Method Germany Internal medicine Pancreatic cancer Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Aged 80 and over Chemotherapy business.industry Middle Aged medicine.disease Gemcitabine 3. Good health Pancreatic Neoplasms Clinical trial Treatment Outcome 030104 developmental biology Oncology Chemotherapy Adjuvant 030220 oncology & carcinogenesis Disease Progression Female Neoplasm Recurrence Local business medicine.drug |
Zdroj: | European Journal of Cancer. 138:172-181 |
ISSN: | 0959-8049 |
Popis: | Background CONKO-006 was designed for patients with pancreatic adenocarcinoma with postsurgical R1 residual status to evaluate the efficacy and safety of the combination of gemcitabine and sorafenib (GemSorafenib) compared with those of gemcitabine + placebo (GemP) for 12 cycles. Patients and methods This randomised, double-blind, placebo-controlled, multicenter study was planned to detect an improvement in recurrence-free survival (RFS) from 42% to 60% after 18 months. Secondary objectives were overall survival (OS), safety and duration of treatment. Results 122 patients were included between 02/2008 and 09/2013; 57 were randomised to GemSorafenib and 65 to GemP. Patient characteristics were wellbalanced (GemSorafenib/GemP) in terms of median age (63/63 years), tumour size (T3/T4: 97/97%), and nodal positivity (86/85%). Grade 3/4 toxicities comprised diarrhoea (GemSorafenib: 12%; GemP: 2%), elevated gamma-glutamyl transferase (GGT) (19%; 9%), fatigue (5%; 2%) and hypertension (5%; 2%), as well as neutropenia (18%; 25%) and thrombocytopenia (9%; 2%). By August 2017, 118 (97%) RFS event had occurred. There were no difference in RFS (median GemSorafenib: 8.5 versus GemP: 9.4 months; p = 0.730) nor OS (median GemSorafenib: 17.6 versus GemP: 17.5 months; p = 0.481). Landmark analyses suggest that patients who received more than six cycles of postoperative chemotherapy had significantly longer OS (p = 0.021). Conclusion CONKO-006 is the first randomised clinical trial to include exclusively patients with PDAC with postsurgical R1 status thus far. Sorafenib added to gemcitabine did neither improve RFS nor OS. However, postoperative treatment exceeding six months seemed to prolong survival and should be further investigated in these high-risk patients. Clinical trial information German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242. |
Databáze: | OpenAIRE |
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