Filippo Pietrantonio1, Chiara Cremolini2, Fausto Petrelli3, Maria Di Bartolomeo4, Fotios Loupakis2, Claudia Maggi4, Carlotta Antoniotti2, Filippo de Braud4, Alfredo Falcone2, Roberto Iacovelli5. 1. Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy. Electronic address: filippo.pietrantonio@istitutotumori.mi.it. 2. Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 3. Azienda Ospedaliera Treviglio, Unità Operativa Oncologia, Treviglio, Bergamo, Italy. 4. Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy. 5. Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy; Department of Radiology, Oncology and Human-Pathology, Sapienza University of Rome, Rome, Italy.
Abstract
BACKGROUND: The use of anti-EGFR monoclonal antibodies (MoAbs) is restricted in Europe to RAS wild-type metastatic colorectal cancer (mCRC) patients. While up today these targeted agents have been mainly chosen as salvage treatment in later lines, their use in first-line in combination with chemotherapy is highly debated. METHODS: MEDLINE/PubMed, Cochrane Library, ASCO University, ESMO/ECCO conferences were searched for randomized controlled trials (RCTs) comparing first-line anti-EGFR MoAbs cetuximab or panitumumab plus chemotherapy to chemotherapy alone or with bevacizumab in patients with RAS wild-type colorectal cancer. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Seven eligible RCTs were identified. In the overall RAS wild-type population (N=2719), anti-EGFR MoAbs significantly improved OS (HR=0.81; 95%CI, 0.71-0.92; p=0.002), PFS (HR=0.77; 95%CI, 0.60-0.98; p=0.03) and objective response rate (ORR) (RR=1.33; 95%CI, 1.09-1.62; p=0.004). The addition of an anti-EGFR MoAb to chemotherapy alone improved PFS (p<0.001) and ORR (p<0.001) with a trend toward longer OS (p=0.07). As compared to bevacizumab, anti-EGFR MoAbs significantly improved OS (HR=0.80; 95%CI, 0.69-0.92; p=0.003), but not PFS (HR=0.94; 95%CI, 0.74-1.19; p=0.59) or ORR (RR=1.10; 95%CI, 0.97-1.25; p=0.12). No significant differences were found with respect to the chemotherapy backbone (oxaliplatin- versus irinotecan-based). CONCLUSIONS: The choice of an anti-EGFR MoAb as first-line biologic is a valid option in RAS wild-type patients candidate to a doublet with infusional 5-FU. While attempting to further refine molecular selection, clinical considerations are crucial in planning the treatment strategy.
BACKGROUND: The use of anti-EGFR monoclonal antibodies (MoAbs) is restricted in Europe to RAS wild-type metastatic colorectal cancer (mCRC) patients. While up today these targeted agents have been mainly chosen as salvage treatment in later lines, their use in first-line in combination with chemotherapy is highly debated. METHODS: MEDLINE/PubMed, Cochrane Library, ASCO University, ESMO/ECCO conferences were searched for randomized controlled trials (RCTs) comparing first-line anti-EGFR MoAbs cetuximab or panitumumab plus chemotherapy to chemotherapy alone or with bevacizumab in patients with RAS wild-type colorectal cancer. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Seven eligible RCTs were identified. In the overall RAS wild-type population (N=2719), anti-EGFR MoAbs significantly improved OS (HR=0.81; 95%CI, 0.71-0.92; p=0.002), PFS (HR=0.77; 95%CI, 0.60-0.98; p=0.03) and objective response rate (ORR) (RR=1.33; 95%CI, 1.09-1.62; p=0.004). The addition of an anti-EGFR MoAb to chemotherapy alone improved PFS (p<0.001) and ORR (p<0.001) with a trend toward longer OS (p=0.07). As compared to bevacizumab, anti-EGFR MoAbs significantly improved OS (HR=0.80; 95%CI, 0.69-0.92; p=0.003), but not PFS (HR=0.94; 95%CI, 0.74-1.19; p=0.59) or ORR (RR=1.10; 95%CI, 0.97-1.25; p=0.12). No significant differences were found with respect to the chemotherapy backbone (oxaliplatin- versus irinotecan-based). CONCLUSIONS: The choice of an anti-EGFR MoAb as first-line biologic is a valid option in RAS wild-type patients candidate to a doublet with infusional 5-FU. While attempting to further refine molecular selection, clinical considerations are crucial in planning the treatment strategy.
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