PULSE, a phase 2 study of mFOLFOX6-panitumumab (P) with biomarker stratification as first-line chemotherapy (CT), in patients (pts) with KRAS (exon 2) metastatic colorectal cancer (mCRC). A GEMCAD 09-03 study

Date

08 Oct 2016

Session

Poster Display

Presenters

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

Author affiliations

  • 1 Medical Oncology, Hospital Clinic y Provincial de Barcelona, 08036 Barcelona - Barcelona/ES
  • 2 Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia/ES
  • 3 Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona/ES
  • 4 Medical Oncology, Hospital Miguel Servet, Zaragoza/ES
  • 5 Medical Oncology, Fundacion Centro Oncologico de Galicia, A Coruna/ES
  • 6 Medical Oncology, Hospital Universitario Arnau Vilanova de Lleida, Lerida/ES
  • 7 Medical Oncology, Hospital de Sabadell Corporacis Parc Tauli, Sabadell/ES
  • 8 Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia/ES
  • 9 Medical Oncology, Hospital General Universitario de Elche, Elche/ES
  • 10 Medical Oncology, Hospital Universitario Morales Meseguer, Murcia/ES
  • 11 Medical Oncology, Hospital Infanta Sofia, Madrid/ES
  • 12 Medical Oncology, Hospital Universitario Son Espases, Palma de Mallorca/ES
  • 13 Medical Oncology, Università di Ferrara, Ferrara/IT
  • 14 Department Of Pathology, Hospital Clinic y Provincial de Barcelona, Barcelona/ES
  • 15 Medical Oncology, Harvard Institutes of Medicine, Boston/US
  • 16 Medical Oncology, Hospital Universitario La Paz, Madrid/ES
More

Resources

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.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings