Long-term treatment of metastatic colorectal cancer with panitumumab.
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ABSTRACT:
SUBMITTER: Lopez-Gomez M
PROVIDER: S-EPMC3296490 | biostudies-other | 2012
REPOSITORIES: biostudies-other
Publications
Long-term treatment of metastatic colorectal cancer with panitumumab.
López-Gómez Miriam M Merino María M Casado Enrique E
Clinical Medicine Insights. Oncology 20120228
Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. More than 30% patients present with metastases at diagnoses and will require systemic chemotherapy. In recent years many anti-EGFR targets have been developed. Among them, panitumumab, a fully human IgG2 monoclonal antibody has shown important benefits in the treatment of this disease. ...[more]
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Project description:Targeted agents are an important therapeutic option in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a recombinant, fully humanized, immunoglobulin G2 monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with efficacy in mCRC as monotherapy and in combination with chemotherapy. Kirsten rat sarcoma (KRAS) mutation status has emerged as an important biomarker to predict response to anti-EGFR therapy. Optimal timing for panitumumab use in the mCRC treatment algorithm has not been established. This review discusses the mechanism of action, predictive biomarkers, and role of panitumumab in the treatment of mCRC.
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Project description:Background:Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Materials and methods:Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided. Results:Tumor sidedness ascertainment (RAS WT population) was 83% (n?=?559/675); 78% of patients (n?=?435) had left-sided and 22% (n?=?124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6?months, adjusted hazard ratio?=?0.73, P?=?0.0112; PEAK: 43.4 versus 32.0?months, adjusted hazard ratio?=?0.77, P?=?0.3125). Conclusion:The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7?months; PEAK 11.4?months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted. Trial registration (Clinicaltrials.gov):PRIME (NCT00364013), PEAK (NCT00819780).
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