Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers.

A targeted therapy is recommended in case of alteration for breast and gastric carcinomas, but miscellaneous other tumor types are 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 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 alteration has been found in 4.7% ( 44/934), including 1.5% ( 14/912) mutations, and 4% ( 30/759) 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% ( 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 mutations ( 2/8, 95% CI 3%-65%, with 2 PR) and 64% for amplifications ( 7/11, 95% CI 31%-89%; with 1 CR, 4 PR, 2 SD). genomic alterations were diffuse across metastatic tumor types and signs of efficacy emerged for HER2 targeted treatments, especially in case of amplifications or a p.S310Y mutation.