TY - JOUR
T1 - Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers
AU - Cabel, Luc
AU - Fuerea, Alina
AU - Lacroix, Ludovic
AU - Baldini, Capucine
AU - Martin, Patricia
AU - Hollebecque, Antoine
AU - Postel-Vinay, Sophie
AU - Varga, Andrea
AU - Balheda, Rastilav
AU - Gazzah, Anas
AU - Michot, Jean Marie
AU - Marabelle, Aurélien
AU - Rouleau, Etienne
AU - Solary, Eric
AU - De Baere, Thierry D.
AU - Angevin, Eric
AU - Armand, Jean Pierre
AU - Michiels, Stefan
AU - Scoazec, Jean Yves
AU - Ammari, Samy
AU - André, Fabrice
AU - Soria, Jean Charles
AU - Massard, Christophe
AU - Verlingue, Loic
N1 - Publisher Copyright:
© Cabel et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - A targeted therapy is recommended in case of ERBB2 alteration for breast and gastric carcinomas, but miscellaneous other tumor types are ERBB2-altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of ERBB2 pathogenic mutation of amplification. Between December 2011 and January 2017 a molecular analysis was performed for 934 patients (759 CGH and 912 tNGS). A novel ERBB2 alteration has been found in 4.7% (n = 44/934), including 1.5% (n = 14/912) ERBB2 mutations, and 4% (n = 30/759) ERBB2 amplifications. A matched HER2 inhibitor was administrated to 70% (31/44) of patients and consisted in trastuzumab plus chemotherapy for 90% of them (28/31). On the 31 evaluable patients, 1 complete response (CR), 10 partial response (PR) and 2 stable disease (SD) > 24 weeks were observed accounting for a clinical benefit rate (CBR) of 42% (n = 13/31, 95% CI 25-61%). Besides breast and oesogastric carcinomas, 19 patients affected by 8 different tumor types had a CBR of 25% for ERBB2 mutations (n = 2/8, 95% CI 3%-65%, with 2 PR) and 64% for ERBB2 amplifications (n = 7/11, 95% CI 31%-89%; with 1 CR, 4 PR, 2 SD).
AB - A targeted therapy is recommended in case of ERBB2 alteration for breast and gastric carcinomas, but miscellaneous other tumor types are ERBB2-altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of ERBB2 pathogenic mutation of amplification. Between December 2011 and January 2017 a molecular analysis was performed for 934 patients (759 CGH and 912 tNGS). A novel ERBB2 alteration has been found in 4.7% (n = 44/934), including 1.5% (n = 14/912) ERBB2 mutations, and 4% (n = 30/759) ERBB2 amplifications. A matched HER2 inhibitor was administrated to 70% (31/44) of patients and consisted in trastuzumab plus chemotherapy for 90% of them (28/31). On the 31 evaluable patients, 1 complete response (CR), 10 partial response (PR) and 2 stable disease (SD) > 24 weeks were observed accounting for a clinical benefit rate (CBR) of 42% (n = 13/31, 95% CI 25-61%). Besides breast and oesogastric carcinomas, 19 patients affected by 8 different tumor types had a CBR of 25% for ERBB2 mutations (n = 2/8, 95% CI 3%-65%, with 2 PR) and 64% for ERBB2 amplifications (n = 7/11, 95% CI 31%-89%; with 1 CR, 4 PR, 2 SD).
KW - ERBB2/HER2 amplification
KW - ERBB2/HER2 mutation
KW - Personalized medicine
KW - Targeted therapy
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?scp=85041699309&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.24188
DO - 10.18632/oncotarget.24188
M3 - Article
C2 - 29515767
AN - SCOPUS:85041699309
SN - 1949-2553
VL - 9
SP - 9741
EP - 9750
JO - Oncotarget
JF - Oncotarget
IS - 11
ER -