511P - Molecular subgroups from the AGITG MAX trial; right or left primary site of colorectal cancer and outcomes for metastatic colorectal cancer (mCRC)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Rectal Cancer
Pathology/Molecular Biology
Presenter Timothy Price
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors T.J. Price1, L. Buizen2, J. Hardingham1, C.K. Lee2, A. Townsend1, M. Bruhn1, R.J. Simes2, K. Wilson2, V. Gebski3, N. Tebbutt4
  • 1Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, 5012 - Woodville South/AU
  • 2Nhmrc Clinical Trials Centre, University of Sydney, 2050 - Sydney/AU
  • 3Biostatistics And Research Methodology, NHMRC Clinical Trials Centre, University of Sydney, 2050 - Sydney/AU
  • 4Austin Health, University of Melbourne, Melbourne/AU

Abstract

Aim

Previous reports have described differences in biology and outcome based on whether the primary is right (R) or left (L) sided. Possible differences in response to biological agents have also been reported based on side of primary lesion.1,2 We have previously published molecular markers from the MAX trial and here we have assessed the panel of markers based on right or left primary site.

Methods

We analysed the MAX trial of capecitabine v capecitabine/bevacizumab (+/-mitomycin C) for differences in patient characteristics, molecular profile and outcomes based on whether the primary was R (caecum to transverse colon) or L (descending colon to rectum) sided. Survival outcomes were analysed using Kaplan-Meier curves and proportional hazards regression modeling.

Results

440 patients had primary site documented and were analysed for baseline characteristics. 298 patients had molecular results. 28% had R sided primary. Major differences between R and L respectively are as follows; female 49% v 33% (p < 0.01), prior history of diabetes 13% v 27% (p = 0.02), lung involvement 28% v 44% (p < 0.01), BRAF MT 16% v 3.5% (p = <0.001), PTEN loss 27.6% v 53% (p = 0.01). All RAS mutation was not statistically higher in R primary, 45% v 37% (p = 0.27). There was no difference in rate of PIK3CA mutation, or high v low expression of assessed angiogenic markers (VEGF, IL-6, IL-8, BFGF, PDGFBB). When comparing R v L, R sided primary predicted for poor outcome for OS: median R = 13.2 v L = 20 months p = 0.001 (HR 0.67, 95% CI 0.53-0.85), but not for PFS (HR 0.96, 95% CI 0.78-1.20). There was no signal that bevacizumab effect differed between R and L primary, PFS for R primary HR 0.82 (95% CI 0.54-1.22) and L primary HR 0.51 (95% CI 0.4-0.63), test for interaction p = 0.10.

Conclusions

There are more negative prognostic factors in patients with R sided primary, in particular high BRAF MT, and these patients have inferior overall survival when compared to those with a L sided primary. There was no suggestion that site of primary had any impact on bevacizumab effect on PFS. 1SY Brule et al, J Clin Oncol 31, 2013 (supp #3528) 2MK Boisen et al, Ann Oncol 24, 2554-59

Disclosure

T.J. Price: Advisory board for Roche. All other authors have declared no conflicts of interest.