549P - Impact of tumour RAS/BRAF status on efficacy of first-line panitumumab + FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Pathology/Molecular Biology
Presenter Meinolf Karthaus
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors M. Karthaus1, R. Hofheinz2, L. Mineur3, R. Greil4, J. Thaler5, E. Fernebro6, F. Overkamp7, H. Kröning8, K.S. Oliner9, J. Terwey10, C.H. Köhne11
  • 1Oncology, Klinikum Neuperlach/Klinikum Harlaching, D81737 - Munich/DE
  • 2Medical Oncology, Universitätsmedizin Mannheim, Universität Heidelberg, 68167 - Mannheim/DE
  • 3Département De Cancérologie Digestive, Institut Sainte-Catherine, 84250 - Avignon/FR
  • 4Iiird Medical Department, University Hospital Salzburg, AT-5020 - Salzburg/AT
  • 5Internal Medicine Iv, Klinikum Wels Grieskirchen, A-4600 - Wels/AT
  • 6Department Of Oncology, Central Hospital, 35185 - Växjö/SE
  • 7Oncologianova Gmbh, Oncoconsult Gbr, Praxis und Tagesklinik für Onkologie, 45657 - Recklinghausen/DE
  • 8Dept. Oncology, Schwerpunktpraxis für Hämatologie und Onkologie, Magdeburg/DE
  • 9Molecular Sciences, Amgen Inc., Newbury Park/US
  • 10Medical Development - Oncology, Amgen (Europe) GmbH, 6301 - Zug/CH
  • 11Department Of Oncology/hematology, Klinikum Oldenburg, Northwest German Cancer Center, 26133 - Oldenburg/DE

Abstract

Aim

Data from a phase III study of second-line panitumumab + FOLFIRI treatment showed that RAS mutations beyond those in KRAS exon 2 impact on the risk/benefit profile of panitumumab in pts with mCRC. Here we report a retrospective RAS/BRAF analysis of a mCRC study of first-line panitumumab + FOLFIRI (NCT00508404).

Methods

In this phase II, single-arm study, first-line panitumumab (6 mg/kg) + FOLFIRI were administered every 14 days until progression to mCRC pts. Objective response rate (ORR) was the primary endpoint. Data were analysed descriptively by tumour RAS/BRAF status. Tumour specimens were assayed for mutations in KRAS exon 2 by DxS and KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 by bidirectional Sanger sequencing.

Results

RAS data were available for 143/154 (93%) pts of whom 69 (48%) had RAS WT (wild-type [WT] for exons 2, 3 and 4 of KRAS/NRAS) and 74 (52%) had RAS mutant (MT) tumours. Overall, median age was 63 years, 62% had primary colon cancer, 55% had moderately differentiated tumours and 76% had ≤2 metastatic sites. Baseline characteristics were generally well balanced between pts with RAS WT vs MT mCRC. ORRs (59% vs 41%; odds ratio: 2.05; 95% confidence interval [CI]: 0.99-4.23) and resection rates (13% vs 9%) were higher in pts with RAS WT vs MT mCRC. Disease control rates were similar (91% vs 92%; odds ratio: 0.93; 95% CI: 0.23-3.66). Longer median duration of response (DoR: 13.0 vs 5.8 months), progression-free survival (PFS: 11.2 vs 7.3 months) and time to progression (TTP: 13.2 vs 7.3 months) were also observed in RAS WT pts. Nine pts (6%) had BRAF MT mCRC. Pts with RAS/BRAF WT (n = 60) vs RAS WT/BRAF MT (n = 83) status had improved ORR (68% vs 36%; odds ratio: 3.81; 95% CI: 1.78-8.22), resection rates (15% vs 8%), median DoR (13.0 vs 5.8 months), PFS (13.2 vs 6.9 months) and TTP (13.3 vs 7.2 months). No new safety signals were identified.

Conclusions

In line with recent studies, consistently favourable efficacy was observed in pts with RAS/BRAF WT vs MT mCRC tumours receiving first-line panitumumab + FOLFIRI treatment. KRAS mutation status appears insufficient for selecting pts for first-line panitumumab + FOLFIRI treatment; tumour RAS analysis aids optimum pt selection.

Disclosure

M. Karthaus: Prof Karthaus has participated in Advisory boards (compensated) for Amgen; L. Mineur: has received research support from Amgen (but not in the context of this abstract), honoraria from Amgen for participation in advisory boards (but not for this study); R. Greil: has received honoraria from Amgen for participation in advisory boards and research support from Amgen (but not in the context of this abstract); J. Thaler: has received honoraria and research funding from Amgen; H. Kröning: did not declare any conflicts of interest; K.S. Oliner: is an Amgen Inc. employee and stockholder; J. Terwey: is an Amgen (Europe) GmbH employee and stockholder; All other authors have declared no conflicts of interest.