Meeting
2016 Gastrointestinal Cancers Symposium
Prospective biomarker validation trial evaluating the prognostic role of the combined expression of phospho-insulin growth factor receptor-1 and matrilysin in KRAS (exon 2) wild-type (WT) metastatic colorectal cancer (mCRC) patients treated with FOLFOX-6 plus panitumumab as first-line therapy [PULSE trial (GEMCAD 09-03)].
Authors
Juan Maurel
Hospital Clinic, Barcelona, Spain
Juan Maurel , Carlos Fernandez-Martos , Marta Martin-Richard , Vicente Alonso , Jose Carlos Mendez , Antonia Salud , Carles Pericay , Jorge Aparicio , Javier Gallego , Alberto Carmona , Enrique Casado , Hermini Manzano , Carlos Horndler , Michele Rubini , Miriam Cuatrecasas , Xabier Garcia-Albeniz , Jaime Feliu
Organizations
Hospital Clinic, Barcelona, Spain, Medical Oncology Department, Fundacion Instituto Valenciano De Oncologia, Valencia, Spain, Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Hospital Universitario Miguel Servet, Zaragoza, Spain, Centro Oncologico de Galicia, A Coruña, Spain, University Hospital Arnau De Vilanova, Lerida, Spain, Hospital de Sabadell, Corporació Sanitària Parc Taulí, Institut Oncològic del Vallès, Sabadell, Spain, Hospital La Fe Oncologia Medica, Valencia, Spain, Servicio de Oncología Médica, Hospital General Universitario de Elche, Elche, Spain, Hospital General Morales Meseguer, Murcia, Spain, Hospital Infanta Sofia, Madrid, Spain, Hospital Son Espases, Palma de Mallorca, Spain, Hospital Miguel Servet, Zaragoza, Spain, Hospital de Ferrara, Ferrara, Italy, Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain, Harvard School of Public Health, Boston, MA, Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain
Research Funding
Other
Background: Matrilysin can activate phospho-insulin growth factor receptor-1 (pIGF-1R) through IGFBP-3 degradation, releasing IGF-1. Matrilysin per se has shown poor prognosis in mCRC and the co-expression of matrilysin and pIGF-1R (double positivity, DP) correlates with poor prognosis in WT KRAS refractory patients (pts) treated with anti-EGFR in retrospective analyses. We performed a prospective clinical trial in WT KRAS (exon 2) pts, treated with FOLFOX plus panitumumab in first-line therapy to validate those findings. Methods: Positive cases were defined by immunohistochemistry as those with moderate or strong intensity (++/+++) and > 70% expression for both matrilysin and p-IGF-1R (antibody anti-pY1316). The primary end-point was progression-free survival (PFS). Seventy-eight pts and 56 events were required to have an 80% power to detect a difference in median PFS of 6 months (two-sided p< 0.05). Results: We screened 196 mCRC pts in 24 centers between Nov/2010 and Apr/2013 and 78 pts met inclusion criteria (42 non-DP and 36 DP). Median follow-up was 23 months. There were no differences in baseline characteristics [age, sex, liver metastases, lactate dehydrogenase (LDH) levels, performance status and BRAF mutational status] between both groups. There were no differences in the number of FOLFOX-6 and panitumumab cycles received. Cutaneous toxicity was more frequent in DP pts (p = 0.035). Response rate was 80.5% in non-DP and 72.2% in DP patients (p = 0.37). Median PFS (95% CI) was 7.4 months (95%CI 5.2-13.3) in non-DP and 9.6 months (95% CI 6.7-17.5, p = 0.15) in DP patients. Median overall survival was 19.8 months (11.5-26.3) in non-DP pts and 39.1 months (26-NE, p = 0.071) in DP pts. Adjusted HR for PFS was 0.68 (95% CI 0.41-1.12). Adjusted analysis for OS was 0.50 (95% CI 0.27-0.90). Conclusions: We found that co-expression of matrilysin and pIGF-1R is a novel strong prognostic biomarker of survival benefit in mCRC KRAS WT pts treated in first-line with FOLFOX-6 plus panitumumab. Clinical trial information: NCT01288339
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session C: Cancers of the Colon, Rectum, and Anus
Track
Cancers of the Colon, Rectum, and Anus
Sub Track
Translational Research
Clinical Trial Registration Number
NCT01288339
Citation
J Clin Oncol 34, 2016 (suppl 4S; abstr 583)
DOI
10.1200/jco.2016.34.4_suppl.583
Abstract #
583
Poster Bd #
E10
Abstract Disclosures
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