| Autor: |
Lucjan Wyrwicz, Kohei Shitara, Josep Tabernero, Sukrut Shah, Pooja Bhagia, Razvan Cristescu, Julie Kobie, Deepti Aurora-Garg, Z. Alexander Cao, Zev A. Wainberg, Joseph Chao, Hugo R. Castro, Jeeyun Lee, Hyun Cheol Chung, Marcelo Garrido, Iveta Kudaba, Charles S. Fuchs, Yung-Jue Bang, Eric Van Cutsem, Keun-Wook Lee |
| Rok vydání: |
2023 |
| Popis: |
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 and Methods: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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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