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Panitumumab vs. Bevacizumab Added to Standard First-Line Chemotherapy
For left-sided, RAS wild-type advanced colorectal cancers, standard care includes first-line chemotherapy combined with either anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) therapy. Retrospective analyses of clinical trials suggest a survival benefit for first-line use of EGFR-targeted agents over the anti-VEGF antibody bevacizumab.
Investigators now report results from the PARADIGM trial from Japan, an industry-sponsored, multicenter, open-label, randomized phase 3 trial in patients with RAS wild-type metastatic colorectal cancer. A total of 802 patients (604 with left-sided primary tumors) were treated with modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) plus either the anti-EGFR antibody panitumumab or bevacizumab every 2 weeks. Sixty-three percent of patients had the primary tumor resected, 50% had a solitary site of disease, and 71% had liver metastases; only 5% received prior adjuvant chemotherapy.
At a median follow-up of 61 months, the primary endpoint of overall survival was superior for panitumumab compared to bevacizumab among patients with left-sided tumors (median, 37.9 vs. 34.3 months; hazard ratio, 0.82; P=0.03), with improved overall survival at 3 years (53% vs. 47%), 4 years (42% vs. 33%), and 5 years (32% vs. 21%). Separation of the survival curves did not occur until after 24 months. Progression-free survival was not significantly different with panitumumab versus bevacizumab (13.1 vs. 11.9 months); the response rate was higher with panitumumab (80% vs. 69%). Rates of grade 3/4 adverse events were higher with panitumumab (72% vs. 65%). More skin toxicity was seen with panitumumab, and more hypertension and epistaxis with bevacizumab.
The PARADIGM trial is the first study powered to demonstrate a survival benefit for EGFR over anti-VEGF targeted agents combined with first-line chemotherapy in RAS wild-type left-sided metastatic colorectal cancer. The modest, late median survival difference of 3 months and initial higher response rate with panitumumab have to be weighed against the greater toxicity of therapy.
Watanabe J et al.
Title: Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial.
Source: JAMA 2023 Apr 18; [e-pub]. (Abstract/FREE Full Text)