Relationships between tumour response and primary tumour location, and predictors of long-term survival, in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab therapy: retrospective analyses of the PRIME and PEAK clinical trials

Marc Peeters, Timothy Price, Julien Taieb, Michael Geissler, Fernando Rivera, Jean-Luc Canon, George Pentheroudakis, Reija Koukakis, Peter Burdon, Salvatore Siena, Marc Peeters, Timothy Price, Julien Taieb, Michael Geissler, Fernando Rivera, Jean-Luc Canon, George Pentheroudakis, Reija Koukakis, Peter Burdon, Salvatore Siena

Abstract

Background: Data from two trials of panitumumab in metastatic colorectal cancer (mCRC) were retrospectively analysed to investigate the effects of primary tumour location on early-tumour shrinkage (ETS) and depth of response (DpR), and identify factors predicting long-term survival.

Methods: Patients with RAS wild-type mCRC from PRIME (NCT00364013) and PEAK (NCT00819780) were included. ETS was defined as a ≥30% reduction in the sum-of-the-longest-diameters of measurable target lesions at eight weeks. DpR was the maximum percentage change from baseline to nadir in patients with shrinkage. Univariate and multivariate logistic analyses of short- versus long-term survivor data were performed.

Results: A total of 435/559 (78%) patients had left-sided disease. Of these, a higher proportion of patients treated with panitumumab versus comparator achieved ETS (PRIME: 62% vs. 36%; PEAK: 58% vs. 41%); median DpR was also higher with panitumumab (PRIME: 59% vs. 49%; PEAK: 70% vs. 48%). In pooled analyses of the studies, more patients with right-sided disease achieved ETS if treated with panitumumab than comparator (39% vs. 29%). Panitumumab treatment consistently predicted long-term survival.

Conclusions: First-line panitumumab was associated with improved ETS and DpR vs. comparator in patients with left-sided mCRC. ETS may identify a subgroup of patients with right-sided disease who might respond to panitumumab.

Conflict of interest statement

M.P. has received research funding from Amgen, Roche and Sirtex, and honoraria from Amgen, Merck Serono, Roche, Sanofi Aventis, Servier and Sirtex. T.P. has acted on advisory boards for Amgen, Merck Serono and Roche, and has received travel support from Amgen. J.T. has acted in consultancy and/or advisory roles for, and received honoraria from Amgen, Baxalta, Celgene, Eli Lilly, Merck, Roche, Sanofi, Servier and Sirtex. Michael Geissler has received research funding and acted in consultancy/advisory roles for Amgen, Bayer, Merck, Roche and Sanofi. F.R. has received research funding from and/or acted on advisory boards for Amgen, Bayer, Celgene, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Roche, Servier and Sanofi. J.-L.C. is a consultant/advisor for Amgen and Roche and has received institutional funding from Amgen, Novartis and Roche. G.P. has received research funding and advisory consulting fees from Amgen, Astra Zeneca, Boehringer, Bristol Myers Squibb, Lilly, Merck, MSD and Roche. R.K. is an employee of Amgen Ltd and owns restricted shares in Amgen. P.B. is an employee of Amgen (Europe) GmbH and owns shares in Amgen. S.S. is a member of advisory boards for Amgen, Bayer, Celgene, Eli Lilly, Ignyta, Merck, Merrimack, Novartis, Roche and Sanofi.

Figures

Fig. 1
Fig. 1
Kaplan–Meier plots showing impact of a primary tumour location and treatment on OS, and b primary tumour location and ETS on OS in pooled analyses from PRIME and PEAK. ETS early-tumour shrinkage, OS overall survival

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