583P - Impact of tumor location on the efficacy of first-line anti-EGFR monoclonal antibody plus chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC): Retrospective analyses of the randomized MACRO-2 and PLANET trials from TTD Group

Abstract

Background: mCRC is a group of heterogeneous diseases rather than a homogeneous one, resulting in clinical and molecular characteristics between right- and left-sided tumors driving to different prognosis. Methods: Pts with KRAS Wild-Type (WT) mCRC treated in 1st-line with EGFR monoclonal antibody inhibitors (EGFRI) plus either FOLFOX or FOLFIRI from two randomized phase II trials (MACRO-2/PLANET) were included in the analysis. Pts were classified according to their primary tumor location as right-sided or left-sided. The main objective was to analyze the effect of primary tumor location on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Differential responses in RAS WT pts according to tumor location were also evaluated. Results: Pts with KRAS WT left-sided primary tumors (N = 209) versus right-sided primary tumors (N = 52) were analyzed. RAS was retrospectively determined in 69% of pts. Both KRAS and RAS WT left-sided had significantly superior ORR, median PFS and median OS compared with right-sided (Table).Table583PKRAS WTRAS WTRight-sided (N = 52)Left-sided (N = 209)Right-sided (N = 33)Left-sided (N = 148)ORR (confirmed)Rate, %25.046.933.352.7OR (95% CI)0.38 (0.19 – 0.75)0.45 (0.20 – 0.99)P-value0.0040.044PFSMedian, m (95% CI)7.209.866.5410.09(4.21 – 11.14)(9.13 – 11.73)(3.91 – 12.58)(9.43 – 12.06)HR (95% CI)0.64 (0.44 – 0.92)0.63 (0.40 – 0.99)P-value0.0160.044OSMedian, m (95% CI)13.5727.7313.5732.79(8.44 – 26.02)(24.97 – 36.17)(8.41 – 34.23)(26.45 – 39.85)HR (95% CI)0.47 (0.33 – 0.67)0.44 (0.28 – 0.68)P-value<0.00010.0002CI: confidence intervals; HR: hazard ratio; m: months; OR: odds ratio; ORR: objective response rate; OS: overall survival; PFS: progression-free survival WT: wild-type. Open table in a new tab CI: confidence intervals; HR: hazard ratio; m: months; OR: odds ratio; ORR: objective response rate; OS: overall survival; PFS: progression-free survival WT: wild-type. Conclusions: Pts with Left-sided primary tumors KRAS or RAS WT mCRC treated with first-line EGFRI plus chemotherapy have significantly improved efficacy outcomes as compared with pts with right-sided primary tumors KRAS or RAS WT mCRC Clinical trial identification: MACRO-2 trial: NCT01161316, PLANET trial: NCT00885885 Legal entity responsible for the study: Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) Funding: Amgen SA (PLANET), Merck. S. L. (MACRO-2) Disclosure: C. Guillen-Ponce: Consultant or advisory role, travel and accommodation: Roche Pharma, Merck Serono. E. Diaz Rubio: Consultant or advisory role, research funding: Bayer, Amgen and Merck. E. Aranda Aguilar: Advisory role: Amgen, Bayer, Celgene, Merck, Roche, Sanofi. All other authors have declared no conflicts of interest.