1. Primary side of origin affects the outcome of mCRC patients treated with first-line FOLFIRI plus bevacizumab independently of BRAF status and mucinous histology
Fotios Loupakis1, Dongyun Yang1, Wu Zhang1, Chiara Cremolini2, Takeru Wakatsuki1, Lisa Salvatore2, Carlotta Antoniotti2, Giuseppe Aprile3,
Marta Schirripa2, Vincenzo Ricci4, Sara Lucchesi5, Gianluca Masi2, Martin Karl Herbert Maus6, Sara Lonardi7, Yan Ning1, Rita El-Khoueiry1, Alfredo Falcone2, Heinz-Josef Lenz1
1.University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; 2.U.O. Oncologia Medica 2.Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy;
3.Azienda Ospedaliero-Universitaria di Udine, Udine, Italy; 4.Unità di Oncologia, Istituto Scientifico San Raffaele, Milano, Italy; 5.U.O. Oncologia Medica, Ospedale , Pontedera, Italy;
6.Department of General-, Visceral- and Tumor Surgery, University of Cologne, Cologne, Germany; 7.Oncologia Medica 1, Istituto Oncologico Veneto - IRCCS, Padova, Italy
Abstract ID: 94778
Background
Results
STUDY POPULATION
The impact of primary tumor’s side on mCRC patients’ clinical outcome is not clear.
Previous experiences are limited by the small sample size, the heterogeneity of included patients and the lack of molecular and hystopathologic data.
Both mucinous histology and BRAF mutations are more frequent in right-sided tumors and are associated to worse prognosis in the metastatic setting
STUDY
POPULATION
N=200
NON-MUC / BRAF wt POPULATION
N=155 N %
Sex
Females 77 37 57
Males
126 63 98
Age
≤65 years
118 59 89
>65 years 82 41 66 43
Primary Site
Right 56 28 36 23
Left
144 72
119
BRAF status
Wild-type
186 93
155
100
Mutated 14 7 /
Mucinous histology
Yes 35 18 No
165
Right (N= 56) median PFS: 9.9 mos
Left (N= 144) median PFS: 12.1 mos
HR: 1.94 [ ] Log-rank test p=0.0001
Right (N= 56) median OS: 24.8 mos
Left (N= 144) median OS: 42.0 mos
HR: 2.26 [ ] Log-rank test p=0.0003
Patients and Methods
At a multivariate analysis, pts with right-side primary were at higher risk of progression (HR=1.88 [95%CI: ], p=0.0026) and death (HR=2.07 [95%CI: ], p=0.006).
455 pts treated with FOLFIRI + BV in a prospective pharmacogenetic study
NON-MUC / BRAF wt POPULATION
Right-sided tumors were more frequently BRAF-mutated (p<0.001).
The association was still significant when adjusting for mucinous histology (p=0.001).
A trend in the association of mucinous histology with right side was observed (p=0.082).
Right (N= 36) median OS: 28.9 mos
Left (N= 119) median OS: 47.6 mos
HR: 1.91 [ ] Log-rank test p=0.022
Right (N= 36) median PFS: 10.0 mos
Left (N= 119) median PFS: 13.0 mos
HR: 1.87 [ ] Log-rank test p=0.003
410 pts evaluable for primary tumor’s side
200 pts evaluable for mucinous histology and BRAF status
STUDY
POPULATION
155 pts with non-mucinous histology and BRAF wild-type status
NON-MUC/BRAF WT
POPULATION
Conclusions
These data underline a possible strong impact of side on the outcome of mCRC treated with first-line FOLFIRI plus bevacizumab. To give a biological explanation for these results, a GWAS on germinal DNA and gene-expression analyses on tumors are ongoing.
In order to clarify the prognostic or predictive role of this feature with regard to antiangiogenic treatments, analyses from 2 phase III randomized trials have been planned.
Tumors were defined as right- or left-sided if they were proximal or distal to the splenic flexure