Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.
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.


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.
Department of Medical Oncology, Centre René Gauducheau, Nantes, France. Electronic address: jean-yves.douillard@ico.unicancer.fr.
J Y
JY
Douillard
Division of Medical Oncology, Ospedale Niguarda Ca' Granda, Milan, Italy.
S
S
Siena
Division of Cancer Sciences and Molecular Pathology, The Beatson West of Scotland Cancer Centre, Glasgow, UK.
J
J
Cassidy
Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
J
J
Tabernero
Department of Medicine, Division of Hematology/Oncology, Mount Sinai Hospital, Toronto, Canada.
R
R
Burkes
Department of Medical Oncology, Hospital de Gastroenterología, Buenos Aires, Argentina.
M
M
Barugel
Department of Medical Oncology, Université Catholique de Louvain, Brussels, Belgium.
Y
Y
Humblet
Department of Oncology, Szent Laszlo Hospital, Budapest, Hungary.
G
G
Bodoky
Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK.
D
D
Cunningham
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
J
J
Jassem
Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
F
F
Rivera
Oncology Department, Masarykuv Onkologicky Ustav, Brno, Czech Republic.
I
I
Kocákova
Department of Medical Oncology, University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa.
P
P
Ruff
Proliferative Diseases Branch, Copernicus Memorial Hospital, Lodz, Poland.
M
M
Błasińska-Morawiec
Department of Oncology, Institut Onkologie a Rehabilitace na Plesi s.r.o., Nová Ves pod Pleší, Czech Republic.
M
M
Šmakal
Department of Oncology and Hematology, Grand Hôpital de Charleroi, Charleroi, Belgium.
J L
JL
Canon
Department of Oncology, The Credit Valley Hospital, Mississauga,Canada.
M
M
Rother
Department of Medical Sciences, Amgen, Inc., Thousand Oaks.
K S
KS
Oliner
Department of Biostatistics, Amgen, Inc., Thousand Oaks.
Y
Y
Tian
Department of Biostatistics, Amgen, Inc., Thousand Oaks.
F
F
Xu
Department of Global Development, Amgen, Inc., Thousand Oaks, USA.
R
R
Sidhu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D011905:Genes, ras; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077544:Panitumumab; D011788:Quality of Life
D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil
FOLFOX; antibody; chemotherapy; metastatic colorectal cancer; panitumumab