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Published on: September 30, 2016
Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data
Martha M Kirstein1, Ansgar Lange1, Anne Prenzler1
1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany.
Background:
Survival of patients with metastatic colorectal cancer (mCRC) has been significantly improved with the introduction of the monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel molecular-targeted agents such as aflibercept and regorafenib have recently been approved. The aim of this review is to summarize and assess the effects of molecular agents in mCRC based on the available phase II and III trials, pooled analyses, and meta-analyses/systematic reviews.
Methods:
A systematic literature search was conducted using the meta-database of the German Institute of Medical Documentation and Information. Criteria of the Scottish Intercollegiate Guidelines Network were used to assess the quality of the controlled trials and systematic reviews/meta-analyses.
Results:
Of the 806 retrieved records, 40 publications were included. For bevacizumab, efficacy in combination with fluoropyrimidine-based chemotherapy in first- and subsequent-line settings has been shown. The benefit of continued VEGF targeting has also been demonstrated with aflibercept and regorafenib. Cetuximab is effective with fluoropyrimidine, leucovorin, and irinotecan (FOLFIRI) in first-line settings and as a single agent in last-line settings. Efficacy for panitumumab has been shown with oxaliplatin with fluoropyrimidine in first-line settings, with FOLFIRI in second-line settings, and as monotherapy in last-line settings. Treatment of anti-EGFR antibodies is restricted to patients with tumors that do not harbor mutations in Kirsten rat sarcoma and in neuroblastoma RAS.
Conclusion:
Among various therapeutic options, the future challenge will be a better selection of the population that will benefit the most from specific anti-VEGF or anti- EGFR treatment and a careful consideration of therapy sequence.
Insights
Molecular agents like anti-VEGF and anti-EGFR therapies have improved survival in metastatic colorectal cancer (mCRC). Future challenges include selecting patients who benefit most from specific treatments and optimizing therapy sequencing.
Area of Science:
- Oncology
- Medical Science
Background:
- Metastatic colorectal cancer (mCRC) survival has improved with targeted therapies.
- Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) inhibitors are key treatments.
- Novel agents like aflibercept and regorafenib are now approved.
Purpose of the Study:
- To review and assess the efficacy of molecular agents in mCRC.
- To analyze data from phase II/III trials, pooled analyses, and meta-analyses.
Main Methods:
- Systematic literature search using the German Institute of Medical Documentation and Information meta-database.
- Quality assessment of trials and reviews using Scottish Intercollegiate Guidelines Network criteria.
Main Results:
- 40 publications were included from 806 retrieved records.
- Bevacizumab, aflibercept, and regorafenib show efficacy in VEGF targeting.
- Cetuximab and panitumumab are effective anti-EGFR agents, with specific usage restrictions based on RAS mutations.
Conclusions:
- Optimizing patient selection for anti-VEGF or anti-EGFR therapy is crucial.
- Careful consideration of treatment sequencing is necessary for maximizing patient benefit.
