Browsing by Author "Yanez, Patricio"

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    A plain language summary of the CheckMate 649 study: nivolumab in combination with chemotherapy compared to chemotherapy alone for untreated advanced or metastatic cancer of the stomach or esophagus
    (2023) Janjigian, Yelena Y.; Shitara, Kohei; Moehler, Markus; Garrido, Marcelo; Salman, Pamela; Wyrwicz, Lucjan; Yamaguchi, Kensei; Skoczylas, Tomasz; Bragagnoli, Arinilda Campos; Liu, Tianshu; Schenker, Michael; Yanez, Patricio; Tehfe, Mustapha; Kowalyszyn, Ruben; Karamouzis, Michalis V.; Bruges, Ricardo; Zander, Thomas; Pazo-Cid, Roberto; Hitre, Erika; Feeney, Kynan; Cleary, James M.; Poulart, Valerie; Cullen, Dana; Lei, Ming; Xiao, Hong; Kondo, Kaoru; Li, Mingshun; Ajani, Jaffer A.
    What is this summary about? This is a summary of the 1-year results of a clinical research study known as CheckMate 649 published in The Lancet in June 2021. The 2-year results on the participants' health and overall quality of life from the same study are in a second publication in Nature in March 2022. Until recently, chemotherapy was the only first treatment option for people with advanced or metastatic gastroesophageal adenocarcinoma who had not been treated before. Patients receiving chemotherapy lived on average for less than 1 year. Nivolumab is an immunotherapy that works by activating a person's immune system to fight back against cancer cells. The goal of CheckMate 649 was to find out if the combination of nivolumab and chemotherapy would help patients with advanced or metastatic gastroesophageal adenocarcinoma live longer and without their cancer getting worse.
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    First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial
    (2021) Janjigian, Yelena Y.; Shitara, Kohei; Moehler, Markus; Garrido, Marcelo; Salman, Pamela; Shen, Lin; Wyrwicz, Lucjan; Yamaguchi, Kensei; Skoczylas, Tomasz; Bragagnoli, Arinilda Campos; Liu, Tianshu; Schenker, Michael; Yanez, Patricio; Tehfe, Mustapha; Kowalyszyn, Ruben; Karamouzis, Michalis V.; Bruges, Ricardo; Zander, Thomas; Pazo-Cid, Roberto; Hitre, Erika; Feeney, Kynan; Cleary, James M.; Poulart, Valerie; Cullen, Dana; Lei, Ming; Xiao, Hong; Kondo, Kaoru; Li, Mingshun; Ajani, Jaffer A.
    Background First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.
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    Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer
    (2022) Shitara, Kohei; Ajani, Jaffer A.; Moehler, Markus; Garrido, Marcelo; Gallardo, Carlos; Shen, Lin; Yamaguchi, Kensei; Wyrwicz, Lucjan; Skoczylas, Tomasz; Bragagnoli, Arinilda Campos; Liu, Tianshu; Tehfe, Mustapha; Elimova, Elena; Bruges, Ricardo; Zander, Thomas; de Azevedo, Sergio; Kowalyszyn, Ruben; Pazo-Cid, Roberto; Schenker, Michael; Cleary, James M.; Yanez, Patricio; Feeney, Kynan; Karamouzis, Michalis, V; Poulart, Valerie; Lei, Ming; Xiao, Hong; Kondo, Kaoru; Li, Mingshun; Janjigian, Yelena Y.
    Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma(1-4). Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial(5) (programmed death ligand-1 (PD-L1) combined positive score >= 5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries(6). Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively(7-)(11). Treatment combining 1 mg kg(-1) nivolumab with 3 mg kg(-1) ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer(12). Here we report both long-term follow-up results comparing nivolumab plus chemotherapyversus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive >= 5 score (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score >= 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.
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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).