PD-014 - First-line treatment with modified FOLFOX6 (mFOLFOX6) + panitumumab or bevacizumab in patients with RAS/BRAF wild-type (WT) metastatic colorectal ca...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter F Rivera
Citation Annals of Oncology (2015) 26 (suppl_4): 101-107. 10.1093/annonc/mdv234
Authors F. Rivera1, R. Koukakis2, M. Karthaus3, J.R. Hecht4, G. Fasola5, J.-. Canon6, G. Demonty7, L. Schwartzberg8
  • 1Hospital Universitario Marques de Valdecilla, Santander/ES
  • 2Amgen Ltd, Uxbridge/UK
  • 3Klinikum Neuperlach, Munich/DE
  • 4David Geffen School of Medicine at UCLA, Santa Monica/US
  • 5University Hospital Santa Maria della Misericordia, Udine/IT
  • 6Grand Hôpital de Charleroi, Charleroi/FR
  • 7Amgen (Europe) GmbH, Zug/CH
  • 8The West Clinic, Memphis/

Abstract

Introduction

In the first-line PEAK study, panitumumab + mFOLFOX6 was associated with significantly longer overall survival (OS) than bevacizumab + mFOLFOX6 in patients with RAS WT mCRC; RECIST overall response rates (ORR) were similar between treatments. Here, we report exploratory analyses of tumour assessments beyond RECIST in the RAS/BRAF WT population of PEAK.

Methods

PEAK was a randomised phase 2 study of panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6 in patients with previously untreated KRAS exon 2 WT mCRC. ORR (investigator assessed), median duration of response (DoR; from first confirmed response to disease progression or death [secondary endpoint]) and depth of response (DpR; the percentage of tumour shrinkage at nadir or progression) in RAS/BRAF WT patients were calculated by treatment. Early tumour shrinkage (ETS) was defined as the proportion of patients with ≥30% tumour shrinkage at week 8 (exploratory analysis).

Results

Overall, 156 patients had RAS/BRAF WT mCRC; 155 were included in the ORR analysis and 143 had tumour shrinkage data available at baseline and week 8. Fourteen patients had RAS WT/BRAF mutant mCRC. Significantly more RAS/BRAF WT patients in the panitumumab + mFOLFOX6 arm had ETS at week 8 compared with the bevacizumab + mFOLFOX6 arm (Table). ORR were similar for the two treatments, while DoR was significantly longer and DpR significantly greater with panitumumab + mFOLFOX6. Median progression-free survival (PFS) was significantly longer in patients with ETS than in those without ETS (12.9 vs 10.6 months; hazard ratio: 0.55 [95% confidence intervals {CI}: 0.37–0.83]; p = 0.004), but was not significantly different between treatments. Of the 14 patients who had RAS WT/BRAF mutant disease, 11 received panitumumab + mFOLFOX6 and three received bevacizumab +mFOLFOX6. Between-treatment trends generally appeared similar to those seen in the RAS/BRAF WT population.

Conclusion

In these exploratory analyses from PEAK, ORR appeared to be similar between treatments but the responses observed appeared to occur earlier, last longer and be deeper in RAS/BRAF WT patients receiving panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6. Median DoR in the panitumumab group appeared to be slightly greater in the RAS/BRAF WT population compared with the RAS WT population (previously reported), whereas results were similar in the bevacizumab group irrespective of tumour BRAF status.

Table: PD-014