Association of Tumor Mutational Burden with Efficacy of Pembrolizumab plus Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study

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dc.contributor.authorLee, Keun-Wook
dc.contributor.authorVan Cutsem, Eric
dc.contributor.authorBang, Yung-Jue
dc.contributor.authorFuchs, Charles S.
dc.contributor.authorKudaba, Iveta
dc.contributor.authorGarrido, Marcelo
dc.contributor.authorChung, Hyun Cheol
dc.contributor.authorLee, Jeeyun
dc.contributor.authorCastro, Hugo R.
dc.contributor.authorChao, Joseph
dc.contributor.authorWainberg, Zev A.
dc.contributor.authorCao, Z. Alexander
dc.contributor.authorAurora-Garg, Deepti
dc.contributor.authorKobie, Julie
dc.contributor.authorCristescu, Razvan
dc.contributor.authorBhagia, Pooja
dc.contributor.authorShah, Sukrut
dc.contributor.authorTabernero, Josep
dc.contributor.authorShitara, Kohei
dc.contributor.authorWyrwicz, Lucjan
dc.date.accessioned2025-01-20T21:04:05Z
dc.date.available2025-01-20T21:04:05Z
dc.date.issued2022
dc.description.abstractPurpose: 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-MS I-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 gas-tric/gastroesophageal junction adenocarcinoma. However, after the exclusion of patients with MSI-H tumors, the clinical utility of TMB was attenuated.
dc.description.funderMerck Sharp Dohme LLC
dc.fuente.origenWOS
dc.identifier.doi10.1158/1078-0432.CCR-22-0121
dc.identifier.eissn1557-3265
dc.identifier.issn1078-0432
dc.identifier.urihttps://doi.org/10.1158/1078-0432.CCR-22-0121
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93209
dc.identifier.wosidWOS:000874854700001
dc.issue.numero16
dc.language.isoen
dc.pagina.final3498
dc.pagina.inicio3489
dc.revistaClinical cancer research
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAssociation of Tumor Mutational Burden with Efficacy of Pembrolizumab plus Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study
dc.typeartículo
dc.volumen28
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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