UPTR remains controversial in the initial management of unresectable asymptomatic mCRC patients (pts), whereas right sidedness is a bad prognostic factor.
Retrospective pooled analysis of KRAS WT mCRC pts treated with 1st line EGFR inhibitors (EGFRI) + chemotherapy (CT) from two phase II randomised trials (MACRO-2 & PLANET). We analysed UPTR effect on overall survival (OS) and progression free survival (PFS) by tumour sidedness (right/left) and stage (I-III/IV) at diagnosis. All stage I-III pts underwent UPTR at diagnosis as standard procedure.
260 pts were included in the analysis (Table). In pts with stage IV at diagnosis, UPTR was associated with a better OS, although differences were only significant in right sided tumours (mOS (m): 20.9 vs 10.6; HR non-UPTR vs UPTR 2.1 (1.0, 4.3); P = 0.038). Conversely, left sided tumours had a significantly better OS vs right sided tumours regardless of UPTR: UPTR HR 0.4 (0.2, 0.8); P = 0.006; no UPTR HR 0.2 (0.1, 0.4); P
In mCRC KRAS WT pts treated in 1st line with EGFRI + CT, UPTR seemed to improve outcomes particularly in right sided tumours. Table: 492P Median (95%CI) OS and PFSTable:
|UPTR||No UPTR||UPTR||No UPTR|
|Stage I-III at diagnosis, N||9||31|
|(30.6 -)||(17.6 -)|
|HR left vs right||1.5 (0.6, 4.1)|
|(8.5, 19.8)||(7.6, 13.9)|
|HR left vs right||1.7 (0.7, 4.2)|
|Stage IV at diagnosis, N||18||24||78||100|
|(5.9, 34.2)||(6.3, 11.8)||(25.3, 45.8)||(20.7, 32.0)|
|HR No UPTR vs UPTR||2.1 (1.0, 4.3)||1.4 (1.0, 2.0)|
|HR left vs right||0.4 (0. 2, 0.8)|
|HR Stage IV vs Stage I-III||4.4 (1.4, 13.9)||1.0 (0.6, 1.8)|
|HR left vs right||0.2 (0.1, 0.4)|
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 S.A. (PLANET) and Merck. S. L. (MACRO-2)
M. Valladares-Ayerbes: Consultant or advisory relationship and honoraria: Roche, Amgen, Merck Serono. A. García-Tapiador: Consultant or advisory role and honoraria: Merck. E. Aranda Aguilar: Advisory role from Amgen, Bayer, Celgene, Merck, Roche, Sanofi. All other authors have declared no conflicts of interest.