Impact of primary tumor sidedness on erlotinib efficacy in patients with metastatic colorectal cancer treated with bevacizumab maintenance: Results from the DREAM phase III trial.
Présenté par le Dr B. CHIBAUDEL - le 20 Janvier 2018
Authors:
Benoist Chibaudel, Thierry Andre, Benoit Samson, Marie-Line Garcia-Larnicol, Jérôme Dauba, Gerard Lledo, Olivier Jean Marie Dupuis, Yves Rinaldi, May Mabro, Nathalie Aucoin, Frédéric Viret, Nicole Tubiana-Mathieu, Ahmed Khalil, Ghaouti Nabil Baba Hamed, Werner Scheithauer, Elisabeth Carola, Dewi Vernerey, Christophe Louvet, Aimery De Gramont, Christophe Tournigand
Background:
Primary tumor sidedness (PTS) could be a predictive maker for treatment efficacy of EGFR inhibitors monoclonal antibodies in patients with wild-type (WT) RAS metastatic colorectal cancer (MCRC), cetuximab having limited efficacy in patients with WT-RAS right-sided tumors. DREAM study demonstrated that adding erlotinib, an oral EGFR tyrosine kinase inhibitor (TKI) to bevacizumab during maintenance therapy improved clinical outcomes (RR, PFS, OS) in patients with MCRC, whatever KRAS status. The aim of this post-hoc analysis is to evaluate the clinical outcomes according to KRAS mutational status and PTS when adding erlotinib to bevacizumab maintenance therapy.
Methods:
PTS was retrospectively collected in patients from the DREAM phase III trial treated with bevacizumab with or without erlotinib as maintenance therapy for MCRC who have been controlled by induction therapy. The limit for the definition of PTS was splenic flexure, and rectal tumors were considered as left-sided tumors. The primary endpoint was overall survival (OS).
Results:
Among 452 patients who received maintenance therapy, PTS ascertainment was 84.7% (n = 383) with 265 (71.0%) patients having left-sided primary tumor and 108 (28.9%) having right-sided primary tumors (3 patients had both and tumor location was unknown in 7 patients). Median OS and treatment effect are presented in table 1.
Conclusions:
The greatest OS benefit of adding erlotinib to bevacizumab maintenance therapy was observed in patients with WT-KRAS and right-sided MCRC, suggesting a clinical impact of the different mechanism of action between EGFR TKI and monoclonal antibodies.
