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Clinical Trial
. 2017 Aug;32(8):1179-1190.
doi: 10.1007/s00384-017-2800-1. Epub 2017 Apr 19.

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma

Fernando Rivera  1 , Meinolf Karthaus  2 , J Randolph Hecht  3 , Isabel Sevilla  4 , Frédéric Forget  5 , Gianpiero Fasola  6 , Jean-Luc Canon  7 , Xuesong Guan  8 , Gaston Demonty  9 , Lee S Schwartzberg  10
Affiliations
Clinical Trial

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma

Fernando Rivera et al. Int J Colorectal Dis. 2017 Aug.

Abstract

Purpose: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).

Methods: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).

Results: One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.

Conclusions: First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

Keywords: Bevacizumab; First-line; Metastatic colorectal cancer; Overall survival; Panitumumab.

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Conflict of interest statement

Conflict of interest

FR has acted on advisory boards and received research funding from Amgen, during the course of this study. He has also acted on advisory boards or received research funding from Bayer, Lilly, Merck-Serono, Merck Sharp and Dohme, Roche, Sanofi, and Servier, outside of the submitted work. MK reports personal fees from Amgen and Roche, outside the submitted work. JRH reports personal fees from Amgen and Roche, outside the submitted work. IS has acted on advisory boards/received honoraria from Amgen, Roche, Merck-Serono, Sanofi, Bayer, Ipsen and Novartis. FF has acted on advisory boards/received honoraria from Novartis and Nutricia, and received research grants from Amgen, outside the submitted work. GF reports grants and personal fees from Amgen, during the course of the study. JLC reports research grants from Amgen, outside the submitted work. XG is an employee of Amgen Inc. GD is an employee of Amgen (Europe) GmbH. LSS has acted as a consultant and on a speaker’s bureau for Amgen, outside the submitted work.

Statement of human rights

PEAK (NCT00819780) was conducted in compliance with the Declaration of Helsinki. The study protocol was approved by an independent ethics committee at each participating study centre.

Informed consent

All patients provided informed consent before any study procedures were performed.

Figures

Fig. 1
Fig. 1
PEAK study CONSORT diagram (data cutoff 11 February 2015)
Fig. 2
Fig. 2
Kaplan-Meier estimates of a Progression-free survival and b Overall survival (RAS wild-type population)
Fig. 3
Fig. 3
Mean (95% confidence interval) percentage change from baseline in tumour load (sum of all target lesions) over time (RAS wild-type population)*
See this image and copyright information in PMC

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