PD-0009 Primary Tumor Location is a Major Independent Prognostic Factor for Mcrc Patients

Abstract

ABSTRACT Introduction Previous attempts to address the question of whether primary tumor location affects outcome of mCRC were limited by small sample size, a high degree of heterogeneity in received treatments, and/or limited information regarding molecular and pathologic features. We performed the present analysis to clarify the prognostic impact of primary tumor location in mCRC patients (pts). Methods Cancers proximal or distal of the splenic flexure were classified as right- or left-sided respectively. Firstly, we tested the association of tumor location with outcome in a cohort of 200 pts treated with FOLFIRI plus bevacizumab within a prospective 1st-line pharmacogenetic study. For these pts data on mucinous histology and BRAF mutational status were available. Secondly, data from two large randomized phase III trials (AVF2107 and NO16966) of first-line chemotherapy plus or minus bevacizumab were used for validation. Primary endpoint was OS. Results In the initial cohort 56 (28.0%) and 144 (72.0%) were right-sided and left-sided respectively. Right-sided cancers had a worse outcome both in terms of PFS and OS (PFS, left vs right: HR = 0.43[95%CI: 0.28-0.66], p = 0.0001; OS: HR = 0.37[95%CI:0.22-0.63], p = 0.0003). A multivariate model confirmed right-sided location as an adverse prognostic variable independent of histology and BRAF mutational status. In the subgroup of non-mucinous and BRAF wild-type tumors (N = 155), pts with right-sided achieved median PFS and OS of 10.0 and 28.9 months compared to 13.0 and 47.6 mos of left-sided (PFS, left vs right: HR = 0.54[95%CI:0.34-0.84], p = 0.003; OS: HR = 0.52[95%CI:0.30-0.93], p = 0.022). In the AVF2107 study, data regarding primary tumor location were available for 559 pts (68.8%). Of these, 353 (63.2%) were left-sided and 206 (36.8%) right-sided. Left-sided cancers achieved a better OS and PFS compared to right-sided (median OS 20.4 vs 14.6 months, HR = 0.55[95%CI: 0.43-0.70], p Conclusion These data suggest a strong prognostic impact of primary tumor location on mCRCs’ outcome. Tumor location did not impact the effect of bevacizumab. Recent data on mRNA signatures suggest a different molecular background for left vs right-sided CRC. Given the consistency of the data across an exploratory set and two confirmatory phase III studies, side of origin should be considered as a stratification factor in future randomized clinical trials in mCRC. Table 1 .