Lee S Schwartzberg1, Fernando Rivera2, Meinolf Karthaus2, Gianpiero Fasola2, Jean-Luc Canon2, J Randolph Hecht2, Hua Yu2, Kelly S Oliner2, William Y Go2. 1. Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA. lschwartzberg@westclinic.com. 2. Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
Abstract
PURPOSE: To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS. PATIENTS AND METHODS: Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety. RESULTS: Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms. CONCLUSION:PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy.
RCT Entities:
PURPOSE: To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS. PATIENTS AND METHODS: Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety. RESULTS: Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms. CONCLUSION: PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy.
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