546P - Tumour shrinkage and response outcomes during 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 Custem11
  • 1Department Of Oncology, Antwerp University Hospital, 2650 - Edegem/BE
  • 2Haematologoy And Oncology, University of Adelaide, 5011 - 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 Clinic Leipzig, University Cancer Center Leipzig, 04103 - Leipzig/DE
  • 8Medical Oncology, Academic Medical Center, University of Amsterdam, 1100 DD - Amsterdam/NL
  • 9Biostatistics, Amgen Ltd, UB8 1DH - Uxbridge/GB
  • 10Medical Development - Oncology, Amgen (Europe) GmbH, 6301 - Zug/CH
  • 11Digestive Oncology, Leuven Cancer Instititue, UZ Leuven, 3000 - Leuven/BE

Abstract

Aim

Tumour shrinkage/response are important outcomes for patients (pts) with metastatic colorectal cancer (mCRC) as they may delay progression and ultimately improve survival. Here we report tumour response data for pts with RAS WT mCRC treated with FOLFIRI ± pmab.

Methods

181 was a phase 3 randomised study of second-line pmab + FOLFIRI vs FOLFIRI alone in pts with previously treated mCRC. KRAS exon 2 wild-type (WT) samples from this study were tested for mutations in KRAS exons 3/4 and NRAS exons 2/3/4 via bidirectional Sanger sequencing and WAVE-based SURVEYOR® to identify pts with RAS WT tumours (no mutations in KRAS/NRAS exons 2, 3 or 4). Objective response rates (ORRs) and median duration of response (DoR) were calculated by treatment. Median progression-free survival (PFS) was calculated for patients with/without ≥30% tumour shrinkage at week (wk) 8.

Results

Overall, 421 pts had RAS WT mCRC. Of these, 411 pts were included in the ORR analysis and 359 had tumour shrinkage data available at baseline and wk 8. More pts in the pmab + FOLFIRI vs FOLFIRI group had ≥30% tumour shrinkage at wk 8 (difference: 30% [95% confidence intervals {CI}: 22-38%]; Table). ORRs were also higher for pmab + FOLFIRI vs FOLFIRI (41% [n = 83] vs 10% [n = 21]; difference 30% [95% CI: 23-38%]). Median DoR was 7.7 vs 9.3 months for pmab + FOLFIRI vs FOLFIRI (hazard ratio [HR]: 1.02 [95% CI: 0.50-2.07]). ≥30% tumour shrinkage at wk 8 correlated with longer median PFS in both treatment groups vs <30% shrinkage (HR: 0.66 [95% CI: 0.47-0.93] for pmab + FOLFIRI and HR: 0.50 [95% CI: 0.24-1.08] for FOLFIRI). Similar results were seen when pts with missing baseline or wk 8 measurements were assumed to have not achieved ≥30% tumour shrinkage at wk 8.

Wk 8 tumour shrinkage, %
<30 ≥30
Pmab + FOLFIRI FOLFIRI Pmab + FOLFIRI FOLFIRI
N (%) 114 (63) 168 (93) 67 (37) 12 (7)
Median PFS, months 6.9 5.5 8.6 8.0

Conclusions

Early tumour shrinkage appears to be correlated with improved PFS in second-line mCRC. More pts with RAS WT tumours achieved ≥30% tumour shrinkage at wk 8 with 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.J. Price: Member of advisory boards for Amgen, Roche and Merck Serono (uncompensated); A. Sobrero: Member of advisory boards and speaker at satellite symposia fora, 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.J.A. Punt: Amgen advisory board member; R. Koukakis: Amgen Ltd employee and stockholder; J. Terwey: Amgen (Europe) GmbH employee and stockholder; E. van Custem: EVC has received research funding from Amgen (paid to University). All other authors have declared no conflicts of interest.