509PD - Primary tumour location (PTL) as a prognostic and predictive factor in advanced colorectal cancer (aCRC): Data from 2075 patients (pts) in randomis...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Colon Cancer
Rectal Cancer
Presenter Jenny Seligmann
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors J.F. Seligmann1, F. Elliott2, S.D. Richman3, K. Southward3, J. Barrett2, P. Quirke3, M. Seymour1
  • 1Department Of Oncology, University of Leeds, LS9 7TF - Leeds/GB
  • 2Department Of Biostatistics, Leeds Institute of Molecular Medicine, Leeds/GB
  • 3Pathology And Tumour Biology, Leeds Institute of Molecular Medicine, Leeds/GB

Abstract

Aim

Variations in tumour biology and outcomes depending upon PTL have been reported in aCRC. We tested effects of PTL in two phase III randomised trials.

Methods

We studied 2075 pts, from FOCUS (1st-line; n = 1390; Lancet 370: 143-52) and PICCOLO (2nd-line; n = 685; Lancet Oncol 14:749-59). We compared: (1) right colon (RC) vs [left colon (LC) or rectum] and (2) LC vs rectum. Association of PTL with RAS/RAF, AREG/EREG and MMR was assessed where available. PTL was tested as a prognostic factor, then for predictive utility by testing PTL/treatment interactions on OS and PFS for: 1st line FU vs doublet (FOCUS); 1st-line irinotecan doublet vs oxaliplatin doublet (FOCUS); 2nd line irinotecan (Ir) +/- panitumumab (Pan) (KRAS-wt pts, PICCOLO).

Results

PTL was RC in 575 (28%), LC in 801 (39%) and rectum in 699 (34%) pts. RC tumours had more BRAF mutations (n = 1136, 22% vs 6%, p < 0.001), lower EREG/AREG expression (n = 323, p < 0.001) and a higher rate of dMMR (n = 688, p < 0.001). In prognostic analysis, RC was associated with worse 1st-line PFS (HR = 1.23, p = 0.05) and OS (HR = 1.44, p < 0.001), independent of BRAF status, but it was not significantly prognostic in 2nd-line. In predictive analysis, no PTL/treatment interactions were seen, with raw data (table) or after adjustment for prognostic factors including BRAF.

Interaction test p-values for treatment comparisons
Comparison Interaction Test p-values
RC vs LC/rectum LC vs Rectum
OS PFS OS PFS
1st line doublet vs single-agent FU (1334 pts) 0.39 0.84 0.48 0.8
1st line OxFU doublet vs IrFU doublet (452 pts) 0.99 0.67 0.18 0.50
2nd line Ir +/- Pan KRAS-WT (450 pts) 0.35 0.13 0.63 0.46
2nd line Ir +/- Pan KRAS/BRAF-WT (341 pts) 0.72 0.89 0.83 0.19

Conclusions

We confirm that RC tumours are biologically distinct, and have worse outcomes with 1st-line therapy. We did not find PTL to be predictive for the benefit of the drugs under test in these trials, so cannot recommend its use for selection of therapy. Better objective predictive biomarkers are required.

Disclosure

All authors have declared no conflicts of interest.