Seligmann, JF, Elliott, F, Richman, S orcid.org/0000-0003-3993-5041 et al. (8 more authors) (2020) Clinical and molecular characteristics and treatment outcomes of advanced right-colon, left-colon and rectal cancers: data from 1180 patients in a phase III trial of panitumumab with an extended biomarker panel. Annals of Oncology, 31 (8). pp. 1021-1029. ISSN 0923-7534
Abstract
Background
Primary tumor location (PTL) is being adopted by clinicians to guide treatment decisions in advanced colorectal cancer (aCRC). Here we test PTL as a predictive marker for panitumumab efficacy, and examine its relationship with an extended biomarker profile. We also examine rectal tumors as a separate location.
Patients and Methods
aCRC patients from the second-line PICCOLO trial of irinotecan versus irinotecan/panitumumab. PTL was classified as right-PTL, left-PTL or rectal-PTL. PTL was assessed as a predictive biomarker for irinotecan /panitumumab (IrPan) effect in RAS-wild-type (RAS-wt) patients (compared with irinotecan alone), then tested for independence alongside an extended biomarker profile (BRAF, epiregulin/amphiregulin (EREG/AREG) and HER3 mRNA expression).
Results
PTL data was available for 1180 patients (98.5%), of which 558 were RAS-wt. High HER3 expression was independently predictive of panitumumab OS improvement, but PTL and EREG/AREG were not.
IrPan PFS improvement compared with irinotecan was seen in left-PTL (HR=0.61,p=0.002) but not right-PTL (HR=0.98,p=0.90)(interaction p=0.05; RAS/BRAF-wt interaction p=0.10), or in rectal-PTL (HR=0.82,p=0.20)(interaction p=0.14 compared with left-PTL; RAS/BRAF-wt interaction p=0.04).
Patients with right-PTL and high EREG/AREG or HER3 expression, had IrPan PFS improvement (high EREG/AREG HR=0.20, p=0.04; high HER3 HR=0.33, p=0.10) compared with irinotecan. Similar effect was seen for rectal-PTL patients (high EREG/AREG HR=0.44, p=0.03; high HER3 HR=0.34, p=0.05).
Conclusions
RAS-wt patients with left-PTL are more likely to have panitumumab PFS advantage than those with right-PTL or rectal-PTL. However, an extended biomarker panel demonstrated significant heterogeneity in panitumumab PFS effect within a tumor location. AREG/EREG and HER3 mRNA expression identifies patients with right-PTL or rectal-PTL who achieve similar PFS effect with panitumumab as left-colon patients. Testing could provide a more reliable basis for clinical decision-making. Further validation and development of these biomarkers is required to optimise routine patient care.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an author produced version of a paper published in Annals of Oncology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | panitumumab; tumour location; epiregulin; amphiregulin; colorectal; precision |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L386 |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 May 2020 15:02 |
Last Modified: | 29 Jul 2022 09:40 |
Status: | Published |
Publisher: | Elsevier BV |
Identification Number: | 10.1016/j.annonc.2020.04.476 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:160907 |