J Y Douillard1, S Siena2, J Cassidy3, J Tabernero4, R Burkes5, M Barugel6, Y Humblet7, G Bodoky8, D Cunningham9, J Jassem10, F Rivera11, I Kocákova12, P Ruff13, M Błasińska-Morawiec14, M Smakal15, J L Canon16, M Rother17, K S Oliner18, Y Tian19, F Xu19, R Sidhu20. 1. Department of Medical Oncology, Centre René Gauducheau, Nantes, France jean-yves.douillard@ico.unicancer.fr. 2. Division of Medical Oncology, Ospedale Niguarda Ca' Granda, Milan, Italy. 3. Division of Cancer Sciences and Molecular Pathology, The Beatson West of Scotland Cancer Centre, Glasgow, UK. 4. Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. 5. Department of Medicine, Division of Hematology/Oncology, Mount Sinai Hospital, Toronto, Canada. 6. Department of Medical Oncology, Hospital de Gastroenterología, Buenos Aires, Argentina. 7. Department of Medical Oncology, Université Catholique de Louvain, Brussels, Belgium. 8. Department of Oncology, Szent Laszlo Hospital, Budapest, Hungary. 9. Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK. 10. Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland. 11. Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 12. Oncology Department, Masarykuv Onkologicky Ustav, Brno, Czech Republic. 13. Department of Medical Oncology, University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa. 14. Proliferative Diseases Branch, Copernicus Memorial Hospital, Lodz, Poland. 15. Department of Oncology, Institut Onkologie a Rehabilitace na Plesi s.r.o., Nová Ves pod Pleší, Czech Republic. 16. Department of Oncology and Hematology, Grand Hôpital de Charleroi, Charleroi, Belgium. 17. Department of Oncology, The Credit Valley Hospital, Mississauga, Canada. 18. Department of Medical Sciences, Amgen, Inc., Thousand Oaks. 19. Department of Biostatistics, Amgen, Inc., Thousand Oaks. 20. Department of Global Development, Amgen, Inc., Thousand Oaks, USA.
Abstract
BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.
RCT Entities:
BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRASmetastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.
Authors: Andreas Lehmann; Josephine H F Wixted; Maxim V Shapovalov; Heinrich Roder; Roland L Dunbrack; Matthew K Robinson Journal: MAbs Date: 2015-09-04 Impact factor: 5.857
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Authors: Aaron P Mitchell; Alan C Kinlaw; Sharon Peacock-Hinton; Stacie B Dusetzina; Hanna K Sanoff; Jennifer L Lund Journal: Oncologist Date: 2019-10-14
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