Browsing by Author "Van Cutsem, Eric"

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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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    Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥ 10
    (2021) Wainberg, Zev A.; Fuchs, Charles S.; Tabernero, Josep; Shitara, Kohei; Muro, Kei; Van Cutsem, Eric; Bang, Yung-Jue; Chung, Hyun Cheol; Yamaguchi, Kensei; Varga, Eniko; Chen, Jen-Shi; Hochhauser, Daniel; Thuss-Patience, Peter; Al-Batran, Salah-Eddin; Garrido, Marcelo; Kher, Uma; Shih, Chie-Schin; Shah, Sukrut; Bhagia, Pooja; Chao, Joseph
    Purpose: Pembrolizumab demonstrated efficacy in PD-L1-positive [combined positive score (CPS) >= 1] advanced gastric/gastro-esophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of dinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS >= 10 in these trials.
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    Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy : JANUS 1 and 2 randomized phase III studies
    (2018) Hurwitz, Herbert; Van Cutsem, Eric; Bendell, Johanna; Hidalgo, Manuel; Chung-Pin Li; Garrido S., Marcelo; Macarulla, Teresa; Sahai, Vaibhav; Sama, Ashwin; Greeno, Edward