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

Journal of Translational Medicine

Alessandro Passardi³  Dino Amadori³  Giovanni Luca Frassineti³  Angela Ragazzini¹  Andrea Casadei Gardini³  Luca Saragoni⁴  Daniele Calistri¹  Sara Bravaccini¹  Paola Rosetti³  Elisa Chiadini¹  Emanuela Scarpi²  Wainer Zoli¹  Martina Valgiusti³  Laura Capelli¹  Paola Ulivi¹ 

[1] Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Via Maroncelli 40, 47014, Meldola (FC), Italy;Unit of Biostatistics and Clinical Trials, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Via Maroncelli 40, 47014, Meldola (FC), Italy;Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Via Maroncelli 40,, 47014, Meldola (FC), Italy;Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy

关键词: PTEN;    PIK3CA;    BRAF;    KRAS;    Cetuximab;    Metastatic colorectal cancer;   

Others  :  1205994
DOI  :  10.1186/1479-5876-10-87

 received in 2012-01-17, accepted in 2012-05-08,  发布年份 2012

【 摘 要 】

Background

KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of KRAS wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen.

Methods

67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry.

Results

BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respectively) and OS (p = 0.008 and p = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for KRAS, BRAF and PIK3CA mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations.

Conclusions

BRAF and PIK3CA mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.

【 授权许可】

   
2012 Ulivi et al.; licensee BioMed Central Ltd.

【 图 表 】

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