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Association of Tumor Mutational Burden with Efficacy of Pembrolizumab±Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study
DC Field | Value | Language |
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dc.contributor.author | Lee, Keun-Wook | - |
dc.contributor.author | Van Cutsem, Eric | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Fuchs, Charles S. | - |
dc.contributor.author | Kudaba, Iveta | - |
dc.contributor.author | Garrido, Marcelo | - |
dc.contributor.author | Chung, Hyun Cheol | - |
dc.contributor.author | Lee, Jeeyun | - |
dc.contributor.author | Castro, Hugo R. | - |
dc.contributor.author | Chao, Joseph | - |
dc.contributor.author | Wainberg, Zev A. | - |
dc.contributor.author | Cao, Z. Alexander | - |
dc.contributor.author | Aurora-Garg, Deepti | - |
dc.contributor.author | Kobie, Julie | - |
dc.contributor.author | Cristescu, Razvan | - |
dc.contributor.author | Bhagia, Pooja | - |
dc.contributor.author | Shah, Sukrut | - |
dc.contributor.author | Tabernero, Josep | - |
dc.contributor.author | Shitara, Kohei | - |
dc.contributor.author | Wyrwicz, Lucjan | - |
dc.date.accessioned | 2022-10-11T01:16:07Z | - |
dc.date.available | 2022-10-11T01:16:07Z | - |
dc.date.created | 2022-09-08 | - |
dc.date.issued | 2022-08 | - |
dc.identifier.citation | Clinical Cancer Research, Vol.28 No.16, pp.3489-3498 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://hdl.handle.net/10371/185726 | - |
dc.description.abstract | © 2022 American Association for Cancer Research.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 firstline 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. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | Association of Tumor Mutational Burden with Efficacy of Pembrolizumab±Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study | - |
dc.type | Article | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-22-0121 | - |
dc.citation.journaltitle | Clinical Cancer Research | - |
dc.identifier.scopusid | 2-s2.0-85136340820 | - |
dc.citation.endpage | 3498 | - |
dc.citation.number | 16 | - |
dc.citation.startpage | 3489 | - |
dc.citation.volume | 28 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Lee, Keun-Wook | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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