Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study

• Published in: Journal of clinical oncology Vol. 28; no. 31; pp. 4697 - 4705
• Main Authors: DOUILLARD, Jean-Yves, SIENA, Salvatore, RIVERA, Fernando, KOCAKOVA, Ilona, RUFF, Paul, BLASINSKA-MORAWIEC, Maria, SMAKAL, Martin, CANON, Jean-Luc, ROTHER, Mark, OLINER, Kelly S, WOLF, Michael, GANSERT, Jennifer, CASSIDY, James, TABERNERO, Josep, BURKES, Ronald, BARUGEL, Mario, HUMBLET, Yves, BODOKY, György, CUNNINGHAM, David, JASSEM, Jacek
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.11.2010
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - genetics; Chemotherapy, Adjuvant; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin - administration & dosage; Leucovorin - adverse effects; Male; Medical sciences; Middle Aged; Mutation; Neoplasm Staging; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Predictive Value of Tests; Prospective Studies; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumors; Antineoplastic agent; Phase III trial; Rectal disease; Panitumumab; Colorectal cancer; Calcium folinate; Monoclonal antibody; Metastasis; Epidermal growth factor receptor; Randomization; Cancerology; Oxaliplatin; Intestinal disease; Clinical trial; Advanced stage; Platinum II Complexes; Fluorouracil; Human; Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; First line treatment; Colonic disease; Alkylating agent; Chemotherapy; Treatment; Antimetabolic; Methyltransferases; Pyrimidine derivatives; Digestive diseases; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2009.27.4860

Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.