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 Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
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.