499P - PULSE, a phase 2 study of mFOLFOX6-panitumumab (P) with biomarker stratification as first-line chemotherapy (CT), in patients (pts) with KRAS (exon...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Cytotoxic agents
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological therapy
Presenter Joan Maurel
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors J. Maurel1, C. Fernández Martos2, M. Martín Richard3, V. Alonso4, C. Méndez Méndez5, A. Salud6, C. Pericay7, J. Aparicio8, J. Gallego9, A. Carmona10, E. Casado11, H. Manzano12, C. Horndler4, M. Rubini13, M. Cuatrecasas14, X. García-Albéniz15, J. Feliu16
  • 1Medical Oncology, Hospital Clinic y Provincial de Barcelona, 08036 Barcelona - Barcelona/ES
  • 2Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia/ES
  • 3Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona/ES
  • 4Medical Oncology, Hospital Miguel Servet, Zaragoza/ES
  • 5Medical Oncology, Fundacion Centro Oncologico de Galicia, A Coruna/ES
  • 6Medical Oncology, Hospital Universitario Arnau Vilanova de Lleida, Lerida/ES
  • 7Medical Oncology, Hospital de Sabadell Corporacis Parc Tauli, Sabadell/ES
  • 8Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia/ES
  • 9Medical Oncology, Hospital General Universitario de Elche, Elche/ES
  • 10Medical Oncology, Hospital Universitario Morales Meseguer, Murcia/ES
  • 11Medical Oncology, Hospital Infanta Sofia, Madrid/ES
  • 12Medical Oncology, Hospital Universitario Son Espases, Palma de Mallorca/ES
  • 13Medical Oncology, Università di Ferrara, Ferrara/IT
  • 14Department Of Pathology, Hospital Clinic y Provincial de Barcelona, Barcelona/ES
  • 15Medical Oncology, Harvard Institutes of Medicine, Boston/US
  • 16Medical Oncology, Hospital Universitario La Paz, Madrid/ES

Abstract

Background

Matrilysin (MMP7) can activate phospho-insulin growth factor receptor-1 (pIGF-1R) through IGFBP-3 degradation, releasing IGF-1. Co-expression of MMP7 and pIGF-1R (double positivity, DP) correlates with poor prognosis in WT KRAS pts treated with anti-EGFR in second-third line therapy. We performed a prospective clinical trial in WT KRAS (exon 2) pts, treated with FOLFOX6-P in first-line CT to validate those findings. A non-planned sub-analysis in the RAS/BRAF WT subset of pts is now presented.

Methods

Positive cases were defined by immunohistochemistry as those with moderate or strong intensity (++ / + ++ ) and >70% expression for both MMP7 and pIGF-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 (m) (two-sided p 

Results

We screened 196 mCRC pts in 24 centers between Nov/2010 and Apr/2013 and 60/78 pts were RAS/BRAF WT (31 non-DP and 29 DP). Median follow-up was 23m. Response rate was 81.7%, mPFS 9.6m (95%CI 7.1-14.1) and median overall survival (OS) 30.4m (95%CI 18.2-39.1).There were no differences in baseline characteristics (age, sex, liver metastases, lactate dehydrogenase (LDH) levels and performance status between both groups). There were no differences in the number of CT cycles received and second-line therapies between both groups. Response rate was 86.2% in non-DP and 77.4% in DP pts (p = 0.74). Median PFS (95% CI) was 9.2m (95%CI 5.2-15.2) in non-DP and 10.5m (95% CI 7.8-18.2, p = 0.16) in DP pts. Median OS was 18.2m (11.2-37.9) in non-DP pts and 39.1m (30-NE, p = 0.11) in DP pts. Adjusted HR for PFS was 0.60 (95% CI 0.31-1.14). Adjusted HR for OS was 0.51 (95% CI 0.27-0.98).

Conclusions

Our study suggest that unexpectedly, co-expression of MMP7 and pIGF-1R, could be a novel strong prognostic biomarker of survival benefit, in mCRC RAS/BRAF WT pts treated in first-line with FOLFOX6-P.

Clinical trial identification

EUdraCT: 2009-017331-18

Legal entity responsible for the study

Grupo Español Multidisciplinar de Cáncer Digestivo (GEMCAD)

Funding

Grupo Español Multidisciplinar de Cáncer Digestivo (GEMCAD)

Disclosure

All authors have declared no conflicts of interest.