| Title: |
Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer |
| Authors: |
Price, TJ; Bruhn, MA; Lee, CK; Hardingham, JE; Townsend, AR; Mann, KP; Simes, J; Weickhardt, A; Wrin, JW; Wilson, K; Gebski, V; Van Hazel, G; Robinson, B; Cunningham, D; Tebbutt, NC |
| Publisher Information: |
NATURE PUBLISHING GROUP |
| Publication Year: |
2015 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
BACKGROUND: Mutations affecting RAS genes are now established predictive markers of nonresponse to anti-EGFR antibodies in advanced CRC. This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab (±mitomycin C) in the randomised phase III MAX study. METHODS: DNA was extracted from archival macrodissected formalin-fixed paraffin-embedded tumour tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS) and correlated with efficacy outcomes. Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM. RESULTS: Of the available 280 of the 471 (59.4%) patients, mutations in KRAS exons 2, 3 and 4 and NRAS 2, 3 and 4 were as follows: 32%, 2.9%, 2.2%, 1.4%, 0.7% and 0% (total RAS MT 39%). The PIK3CA MT rate was 7.5% exon 9 and 3.6% exon 20. Extended RAS gene mutation status (WT vs MT) had no prognostic impact for PFS (HR 0.91 (0.71-1.17)) or OS (HR 0.95 (0.71-1.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.37-0.85) for RAS MT and HR 0.69 (0.5-0.97) for RAS WT; P for interaction 0.50). The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic. CONCLUSION: Of KRAS exon 2 WT patients, 10% had additional RAS mutations. Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS, or predictive of bevacizumab outcome in patients with advanced CRC. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0007-0920 |
| Relation: |
pii: bjc201537; https://hdl.handle.net/11343/304083 |
| Availability: |
https://hdl.handle.net/11343/304083 |
| Rights: |
https://creativecommons.org/licenses/by-nc-sa/4.0 ; CC BY-NC-SA |
| Accession Number: |
edsbas.7B8E9809 |
| Database: |
BASE |