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. 2016 Nov 8;115(10):1215-1222.
doi: 10.1038/bjc.2016.343. Epub 2016 Oct 20.

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer

Meinolf Karthaus  1 , Ralf-Dieter Hofheinz  2 , Laurent Mineur  3 , Henry Letocha  4 , Richard Greil  5 , Josef Thaler  6 , Eva Fernebro  7 , Kelly S Oliner  8 , Michael Boedigheimer  9 , Brian Twomey  9 , Ying Zhang  9 , Gaston Demonty  10 , Claus-Henning Köhne  11
Affiliations

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer

Meinolf Karthaus et al. Br J Cancer. .

Abstract

Background: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC).

Methods: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression.

Results: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression.

Conclusions: First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated.

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Conflict of interest statement

MK is an advisor for, and has received honoraria from, Amgen Ltd. R-DH has received honoraria from Amgen Ltd. LM is an advisor for, and has received honoraria and research funding from, Amgen. HL has acted as a consultant/advisor for Amgen Ltd & Roche Ltd. RG has received research support from Amgen. JT has received honoraria and research funding from Amgen Ltd. KSO is a former employee of Amgen Inc. MB, BT, YZ, GD are employees of Amgen Inc. C-HK has acted as a consultant/advisor to Amgen Ltd, Merck KG Darmstadt & Roche Ltd. EF declares no conflict of interest.

Figures

Figure 1
Figure 1
Duration of response by tumour RAS status.
Figure 2
Figure 2
Progression-free survival by tumour (A) RAS and (B) RAS/BRAF status.
See this image and copyright information in PMC

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