Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

• Main Authors: Ulivi Paola, Capelli Laura, Valgiusti Martina, Zoli Wainer, Scarpi Emanuela, Chiadini Elisa, Rosetti Paola, Bravaccini Sara, Calistri Daniele, Saragoni Luca, Gardini Andrea, Ragazzini Angela, Frassineti Giovanni, Amadori Dino, Passardi Alessandro
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: Journal of Translational Medicine
• Subjects: Metastatic colorectal cancer; Cetuximab; KRAS; BRAF; PIK3CA; PTEN
• Online Access: http://www.translational-medicine.com/content/10/1/87

<p>Abstract</p> <p>Background</p> <p><it>KRAS</it> mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of <it>KRAS</it> wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding <it>KRAS</it> WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of <it>KRAS</it>, <it>BRAF</it>, <it>PIK3CA</it> and PTEN expression in mCRC patients treated with a cetuximab-based regimen.</p> <p>Methods</p> <p>67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of <it>KRAS</it> and exon 15 of <it>BRAF</it> were analyzed by direct sequencing, <it>PIK3CA</it> was evaluated by pyrosequencing and PTEN expression by immunohistochemistry.</p> <p>Results</p> <p><it>BRAF</it> and <it>PIK3CA</it> mutations were independently associated with worse PFS (<it>p</it> = 0.006 and <it>p</it> = 0.028, respectively) and OS (<it>p</it> = 0.008 and <it>p</it> = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for <it>KRAS</it>, <it>BRAF</it> and <it>PIK3CA</it> mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations.</p> <p>Conclusions</p> <p><it>BRAF</it> and <it>PIK3CA</it> mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.</p>