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Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer

Journal for ImmunoTherapy of Cancer Feb 04, 2019

Mishima S, et al. - Researchers analyzed clinicopathological and molecular features of nivolumab responders among 80 patients (pts) with advanced gastric cancer (AGC) who were treated with nivolumab after two or more chemotherapy regimens in a single institution from September 2017 to May 2018. Using immunohistochemistry, they analyzed PD-L1 (Programmed death-ligand 1) expression in tumor cells (TC) and mismatch repair (MMR). More than 10 mutations/megabase defined a high tumor mutation burden (TMB). A total of 72 pts with measurable lesions were assessed for tumor response and 14 pts (19%) had an objective response. They found markedly higher overall response rate (ORR) in pts with Eastern Cooperative Oncology Group performance status (ECOGPS) 0 in those with PS 1 or 2, MMR-deficient (MMR-D) in those with MMR-proficient (MMR-P), PD-L1+ in TC in those with PD-L1- in TC and PIK3CA mutation in those with PIK3CA wild-type. In pts with at least one of the following factors; MMR-D, high TMB, Epstein-Barr virus (EBV)+ and PD-L1+ in TC, the observed ORR was 31% as compared with 0% observed in those without these factors. A significantly longer progression-free survival was observed in pts with PS 0 vs in those with PS 1 or 2, MMR-D vs in those with MMR-P, and PD-L1+ in TC vs in those with PD-L1- in TC. Overall, some features were related to favorable response to nivolumab for AGC and for efficacy prediction, combining these features might have utility.
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