Medline ® Abstract for Reference 232
of 'Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials'
PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer.
Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, Yu H, Oliner KS, Go WY
J Clin Oncol. 2014;32(21):2240. Epub 2014 Mar 31.
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.
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. email@example.com.