548P - Impact of baseline covariates and prior therapy on the efficacy of second-line panitumumab (pmab) + FOLFIRI vs FOLFIRI treatment

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Colon and Rectal Cancer
Therapy
Biological therapy
Presenter Marc Peeters
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors M. Peeters1, T.J. Price2, A. Cervantes Ruiperez3, A. Sobrero4, M. Ducreux5, T. André6, F. Lordick7, C.J.A. Punt8, R. Koukakis9, J. Terwey10, E. Van Cutsem11
  • 1Department Of Oncology, Antwerp University Hospital, 2650 - Edegem/BE
  • 2Haematology And Oncology, Queen Elizabeth Hospital, Woodville/AU
  • 3Incliva Biomedical Research Institute, Hospital Clínico de Valencia, University of Valencia, 46010 - Valencia/ES
  • 4Medical Oncology, IRCCS Ospedale San Martino IST, 16132 - Genova/IT
  • 5Gi Unit, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 6Department Of Medical Oncology, Hôpital Saint Antoine, FR-75012 - Paris/FR
  • 7University Cancer Center Leipzig, University of Leipzig, 04103 - Leipzig/DE
  • 8Department Of Medical Oncology, Academic Medical Center, University of Amsterdam, 1100DD - Amsterdam/NL
  • 9Biostatistics, Amgen Ltd, UB8 1DH - Uxbridge/GB
  • 10Medical Development - Oncology, Amgen (Europe) GmbH, 6301 - Zug/CH
  • 11Digestive Oncology, Leuven Cancer Institute, UZ Leuven, 3000 - Leuven/BE

Abstract

Aim

Expanding RAS analyses beyond KRAS exon 2 is important in selecting patients (pts) for pmab treatment. Here we present prespecified subgroup analyses from a phase 3 randomised second-line pmab + FOLFIRI vs FOLFIRI study in metastatic colorectal cancer (mCRC) pts.

Methods

Progression-free (PFS) and overall survival (OS) were co-primary endpoints. KRAS exon 2 wild-type (WT) samples were tested for mutations in KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 via bidirectional Sanger sequencing and WAVE-based SURVEYOR®. PFS and OS subgroup analyses were performed by randomisation stratification factors (ECOG performance status [PS], prior bevacizumab [bev]/prior oxaliplatin [ox] for mCRC) and prespecified baseline covariates (age, BRAF status).

Results

Overall, 18% (107/597) of KRAS exon 2 WT pts had other RAS mutations. In RAS WT pts overall (n = 421), PFS was significantly longer in the pmab + FOLFIRI vs FOLFIRI arm (hazard ratio [HR]: 0.70 [95% confidence intervals {CI}: 0.54-0.91]; p = 0.0069). RAS WT pts <65 years (n = 263; HR: 0.64 [95% CI: 0.45-0.89]; p = 0.0089), with an ECOG PS of 0/1 (n = 400; HR: 0.68 [95% CI: 0.52-0.88]; p = 0.0042), with BRAF WT mCRC (n = 376; HR: 0.68 [95% CI: 0.51-0.90]; p = 0.0063), who had received prior ox (n = 284; HR: 0.64 [95% CI: 0.47-0.86]; p = 0.0035) or no prior bev (n = 348; HR: 0.72 [95%CI: 0.54-0.95]; p = 0.0204) had significantly longer PFS with pmab + FOLFIRI vs FOLFIRI. PFS improvements were seen in the pmab + FOLFIRI group in all other subgroups assessed except for those with ECOG PS 2 (n = 21). OS analyses gave similar results, but significant OS benefits were seen in pmab + FOLFIRI vs FOLFIRI-treated pts who had received prior ox (HR: 0.74 [95% CI: 0.56-0.98]; p = 0.0391) or prior bev (HR: 0.45 [95% CI: 0.24-0.88]; p = 0.0185).

Median PFS, months
Pmab + FOLFIRI (n = 208) FOLFIRI (n = 213)
Age
<65 yrs 6.4 4.6*
≥65 yrs 6.4 3.9
ECOG PS
0/1 6.7 4.6*
2 3.1 3.5
BRAF MT
Yes 2.5 1.8
No 6.9 5.5*
Prior ox
Yes 6.1 3.7*
No 6.7 6.9
Prior bev
Yes 6.7 3.7
No 6.1 4.6*

*p < 0.05

Conclusions

Consistent PFS benefits were observed across all subgroups in pts with RAS WT mCRC receiving second-line pmab + FOLFIRI vs FOLFIRI alone.

Disclosure

M. Peeters: Consultant/advisory roles for Amgen (all compensated) and has also received honoraria and research funding from Amgen; T. Price: Member of advisory boards for Amgen, Roche and Merck Serono (uncompensated); A. Sobrero: Member of advisory boards and speaker at satellite symposia for Celgene, Bayer, Sanofi, Merck, Roche, and Amgen; M.P. Ducreux: Member of advisory boards for Amgen, Merck, Roche, participation in symposium for Amgen, Merck, Roche; T. André: Advisory board membership and honoraria from Amgen; C. Punt: Amgen advisory board member; R. Koukakis: Amgen Ltd employee and stockholder;J. Terwey: Amgen (Europe) GmbH employee and stockholder; E. Van Cutsem: Has received research funding from Amgen (paid to University). All other authors have declared no conflicts of interest.