Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
/ therapeutic use
B7-H1 Antigen
/ metabolism
Biomarkers, Tumor
/ genetics
DNA Mismatch Repair
Female
Herpesvirus 4, Human
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Nivolumab
/ therapeutic use
Stomach Neoplasms
/ drug therapy
Gastric cancer
Nivolumab
PD-1 inhibitor
Predictive factor
Responders
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
31 01 2019
31 01 2019
Historique:
received:
16
10
2018
accepted:
20
01
2019
entrez:
2
2
2019
pubmed:
2
2
2019
medline:
2
4
2020
Statut:
epublish
Résumé
Clinicopathological and molecular features of responders to nivolumab for advanced gastric cancer (AGC) are not well understood. Patients (pts) with AGC who were treated with nivolumab after two or more chemotherapy regimens in a single institution from September 2017 to May 2018 were enrolled in this study. PD-L1 expression in tumor cells (TC) and mismatch repair (MMR) were analyzed by immunohistochemistry. Epstein-Barr virus (EBV) was detected by in situ hybridization. Cancer genome alterations were evaluated by a next-generation sequencing-based panel. High tumor mutation burden (TMB) was defined as more than 10 mutations/megabase. A total of 80 pts were analyzed in this study. Tumor response was evaluated in 72 pts with measurable lesions and 14 pts (19%) had an objective response. Overall response rate (ORR) was significantly higher in pts with 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. ORR was 31% in pts with at least one of the following factors; MMR-D, high TMB, EBV+ and PD-L1+ in TC vs. 0% in those without these factors. Progression-free survival was significantly longer in pts with PS 0 than in those with PS 1 or 2, MMR-D than in those with MMR-P, and PD-L1+ in TC than in those with PD-L1- in TC. Some features were associated with favorable response to nivolumab for AGC. Combining these features might be useful to predict efficacy.
Sections du résumé
BACKGROUND
Clinicopathological and molecular features of responders to nivolumab for advanced gastric cancer (AGC) are not well understood.
METHODS
Patients (pts) with AGC who were treated with nivolumab after two or more chemotherapy regimens in a single institution from September 2017 to May 2018 were enrolled in this study. PD-L1 expression in tumor cells (TC) and mismatch repair (MMR) were analyzed by immunohistochemistry. Epstein-Barr virus (EBV) was detected by in situ hybridization. Cancer genome alterations were evaluated by a next-generation sequencing-based panel. High tumor mutation burden (TMB) was defined as more than 10 mutations/megabase.
RESULTS
A total of 80 pts were analyzed in this study. Tumor response was evaluated in 72 pts with measurable lesions and 14 pts (19%) had an objective response. Overall response rate (ORR) was significantly higher in pts with 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. ORR was 31% in pts with at least one of the following factors; MMR-D, high TMB, EBV+ and PD-L1+ in TC vs. 0% in those without these factors. Progression-free survival was significantly longer in pts with PS 0 than in those with PS 1 or 2, MMR-D than in those with MMR-P, and PD-L1+ in TC than in those with PD-L1- in TC.
CONCLUSIONS
Some features were associated with favorable response to nivolumab for AGC. Combining these features might be useful to predict efficacy.
Identifiants
pubmed: 30704511
doi: 10.1186/s40425-019-0514-3
pii: 10.1186/s40425-019-0514-3
pmc: PMC6357506
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
Nivolumab
31YO63LBSN
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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