Browsing by Author "Lee, Jeeyun"

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    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
    (2022) Lee, Keun-Wook; Van Cutsem, Eric; Bang, Yung-Jue; Fuchs, Charles S.; Kudaba, Iveta; Garrido, Marcelo; Chung, Hyun Cheol; Lee, Jeeyun; Castro, Hugo R.; Chao, Joseph; Wainberg, Zev A.; Cao, Z. Alexander; Aurora-Garg, Deepti; Kobie, Julie; Cristescu, Razvan; Bhagia, Pooja; Shah, Sukrut; Tabernero, Josep; Shitara, Kohei; Wyrwicz, Lucjan
    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-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.
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    Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial
    (2020) Shitara, Kohei; Van Cutsem, Eric; Bang, Yung-Jue; Fuchs, Charles; Wyrwicz, Lucjan; Lee, Keun-Wook; Kudaba, Iveta; Garrido, Marcelo; Chung, Hyun Cheol; Lee, Jeeyun; Castro, Hugo Raul; Mansoor, Wasat; Braghiroli, Maria Ignez; Karaseva, Nina; Caglevic, Christian; Villanueva, Luis; Goekkurt, Eray; Satake, Hironaga; Enzinger, Peter; Alsina, Maria; Benson, Al; Chao, Joseph; Ko, Andrew H.; Wainberg, Zev A.; Kher, Uma; Shah, Sukrut; Kang, S. Peter; Tabernero, Josep
    IMPORTANCE Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.
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    Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial
    (2023) Rha, Sun Young; Oh, Do-Youn; Yanez, Patricio; Bai, Yuxian; Ryu, Min-Hee; Lee, Jeeyun; Rivera, Fernando; Alves, Gustavo Vasconcelos; Garrido, Marcelo; Shiu, Kai-Keen; Fernandez, Manuel Gonzalez; Li, Jin; Lowery, Maeve A.; Cil, Timucin; Cruz, Felipe Melo; Qin, Shukui; Luo, Suxia; Pan, Hongming; Wainberg, Zev A.; Yin, Lina; Bordia, Sonal; Bhagia, Pooja; Wyrwicz, Lucjan S.
    Background: PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.Methods: KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m(2) per day) administered continuously on days 1-5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m(2)) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m(2)) administered twice daily on days 1-14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m(2)) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete.Findings: Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]).Median follow-up at the data cutoff was 310 months (IQR 230-383). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (129 months [95% CI 119-140] vs 115 months [106-121]; hazard ratio [HR] 078 [95% CI 070-087]; p<00001), in participants with a PD-L1 CPS of 1 or higher (130 months [116-142] vs 114 months [105-120]; 074 [065-084]; p<00001), and in participants with a PD-L1 CPS of 10 or higher (157 months [138-193] vs 118 months [103-127]; 065 [053-079]; p<00001).