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.
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.
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).
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 mCRCTable:
|KRAS WT||RAS WT|
|Right-sided (N = 52)||Left-sided (N = 209)||Right-sided (N = 33)||Left-sided (N = 148)|
|OR (95% CI)||0.38 (0.19 – 0.75)||0.45 (0.20 – 0.99)|
|Median, m (95% CI)||7.20||9.86||6.54||10.09|
|(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)|
|Median, m (95% CI)||13.57||27.73||13.57||32.79|
|(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)|
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)
Amgen SA (PLANET), Merck. S. L. (MACRO-2)
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.