Association of Tumor Mutational Burden with Efficacy of Pembrolizumab±Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study.
Clin Cancer Res
; 28(16): 3489-3498, 2022 08 15.
Article
in En
| MEDLINE
| ID: mdl-35657979
ABSTRACT
PURPOSE:
This prespecified exploratory analysis evaluated the association between tumor mutational burden (TMB) status and outcomes of first-line pembrolizumab±chemotherapy versus chemotherapy in KEYNOTE-062. PATIENTS ANDMETHODS:
In patients with advanced gastric cancer and evaluable TMB data, we evaluated the association between TMB (continuous variable; square root scale) assessed with FoundationOne CDx and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)] using logistic (ORR) and Cox proportional hazards (PFS, OS) regression models. Clinical utility of TMB was assessed using the prespecified cutoff of 10 mut/Mb.RESULTS:
TMB data were available for 306 of 763 patients (40.1%; pembrolizumab, 107; pembrolizumab+chemotherapy, 100; chemotherapy, 99). TMB was significantly associated with clinical outcomes in patients treated with pembrolizumab and pembrolizumab+chemotherapy (ORR, PFS, and OS; all P < 0.05) but not with chemotherapy (all P > 0.05). The overall prevalence of TMB ≥10 mut/Mb was 16% across treatment groups; 44% of patients who had TMB ≥10 mut/Mb had high microsatellite instability (MSI-H) tumors. Improved clinical outcomes (ORR, PFS, and OS) were observed in pembrolizumab-treated patients (pembrolizumab monotherapy and pembrolizumab+chemotherapy) with TMB ≥10 mut/Mb. When the analysis was limited to the non-MSI-H subgroup, both the positive association between clinical outcomes with pembrolizumab or pembrolizumab+chemotherapy and TMB as a continuous variable and the clinical utility of pembrolizumab (with or without chemotherapy) versus chemotherapy by TMB cutoff were attenuated.CONCLUSIONS:
This exploratory analysis of KEYNOTE-062 suggests an association between TMB and clinical efficacy with first-line pembrolizumab-based therapy in patients with advanced gastric/gastroesophageal junction adenocarcinoma. However, after the exclusion of patients with MSI-H tumors, the clinical utility of TMB was attenuated.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
/
Antibodies, Monoclonal, Humanized
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Clin Cancer Res
Year:
2022
Document type:
Article