Predictive role of microsatellite instability for PD-1 blockade in patients with advanced gastric cancer: a meta-analysis of randomized clinical trials.
advanced gastric cancer
immune checkpoint inhibitors
meta-analysis
microsatellite instability
randomized clinical trials
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
28
11
2020
revised:
08
12
2020
accepted:
10
12
2020
pubmed:
19
1
2021
medline:
30
10
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
Several post hoc analyses of randomized controlled trials (RCTs) suggested the importance of microsatellite instability (MSI) as a positive predictive factor to immunotherapy in patients with advanced gastric cancer (GC); however, individually these have low statistical power. RCTs investigating treatment with or without an anti-programmed cell death protein 1 (PD-1) agent for advanced GC and providing outcome according to MSI status were selected. The hazard ratio (HR) and the odds ratio were used to compare the treatment effect on survival outcomes and tumor response, respectively, for anti-PD-1-based therapy compared with standard therapy. Evidence for treatment effect by MSI status was evaluated by a test of interaction. The phase III KEYNOTE-062, CheckMate-649, JAVELIN Gastric 100 and KEYNOTE-061 trials were included. A total of 2545 patients with evaluable MSI status were included and 123 (4.8%) had MSI-high cancers. The HR for overall survival benefit with anti-PD-1-based regimens was 0.34 (95% CI: 0.21-0.54) for MSI-high cancers versus 0.85 [95% confidence interval (CI): 0.71-1.00] for microsatellite stable. The treatment effect was significantly different in the two subgroups (P for interaction 0.003). In the MSI-high subgroup, the HR for progression-free survival was 0.57 (95% CI: 0.33-0.97; P = 0.04) and the odds ratio for response was 1.76 (95% CI: 1.10-2.83; P = 0.02). Patients with MSI-high GC should be regarded as a specific and highly immunosensitive population worthy of dedicated clinical trials.
Sections du résumé
BACKGROUND
Several post hoc analyses of randomized controlled trials (RCTs) suggested the importance of microsatellite instability (MSI) as a positive predictive factor to immunotherapy in patients with advanced gastric cancer (GC); however, individually these have low statistical power.
METHODS
RCTs investigating treatment with or without an anti-programmed cell death protein 1 (PD-1) agent for advanced GC and providing outcome according to MSI status were selected. The hazard ratio (HR) and the odds ratio were used to compare the treatment effect on survival outcomes and tumor response, respectively, for anti-PD-1-based therapy compared with standard therapy. Evidence for treatment effect by MSI status was evaluated by a test of interaction.
RESULTS
The phase III KEYNOTE-062, CheckMate-649, JAVELIN Gastric 100 and KEYNOTE-061 trials were included. A total of 2545 patients with evaluable MSI status were included and 123 (4.8%) had MSI-high cancers. The HR for overall survival benefit with anti-PD-1-based regimens was 0.34 (95% CI: 0.21-0.54) for MSI-high cancers versus 0.85 [95% confidence interval (CI): 0.71-1.00] for microsatellite stable. The treatment effect was significantly different in the two subgroups (P for interaction 0.003). In the MSI-high subgroup, the HR for progression-free survival was 0.57 (95% CI: 0.33-0.97; P = 0.04) and the odds ratio for response was 1.76 (95% CI: 1.10-2.83; P = 0.02).
CONCLUSIONS
Patients with MSI-high GC should be regarded as a specific and highly immunosensitive population worthy of dedicated clinical trials.
Identifiants
pubmed: 33460964
pii: S2059-7029(20)32902-1
doi: 10.1016/j.esmoop.2020.100036
pmc: PMC7815473
pii:
doi:
Substances chimiques
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
100036Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Disclosure FP reports personal fees from Amgen, Roche, Sanofi, Bayer, Servier, Merck-Serono, Lilly; advisory role with Amgen, Bayer, Servier, Merk-Serono and research grants from Bristol-Myers Squibb. AIRC under IG 2019 - ID. 23624 project – P.I. Pietrantonio Filippo. JC reports grants and personal fees from Merck, Amgen, Macrogenics, Ono Pharmaceuticals, Foundation Medicine, Daiichi-Sankyo and Bristol Myers Squibb. ES reports personal fees from AstraZeneca, Astellas, Bristol Myers Squibb, Celgene, Five Prime, Gritstone, Merck, Roche, Servier and Zymworks. The other authors have declared no conflicts of interest.