Browsing by Author "Cleary, James M."

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    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.
  • No Thumbnail Available
    Item
    First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial
    (2024) Janjigian, Yelena Y.; Ajani, Jaffer A.; Moehler, Markus; Shen, Lin; Garrido, Marcelo; Gallardo, Carlos; Wyrwicz, Lucjan; Yamaguchi, Kensei; Cleary, James M.; Elimova, Elena; Karamouzis, Michalis; Bruges, Ricardo; Skoczylas, Tomasz; Bragagnoli, Arinilda; Liu, Tianshi; Tehfe, Mustapha; Zander, Thomas; Kowalyszyn, Ruben; Pazo-Cid, Roberto; Schenker, Michael; Feeny, Kynan; Wang, Rui; Lei, Ming; Chen, Clara; Nathani, Raheel; Shitara, Kohei
    Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal adenocarcinoma were randomly assigned to nivolumab plus chemotherapy or chemotherapy. Primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors expressed PD-L1 combined positive score (CPS) >= 5. With 36.2-month minimum follow-up, for patients with PD-L1 CPS >= 5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81); 21% versus 10% of patients were alive at 36 months, respectively; the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively. The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy; median duration of response was 9.6 months (95% CI, 8.2 to 12.4) versus 7.0 months (95% CI, 5.6 to 7.9), respectively. Nivolumab plus chemotherapy also continued to show improvement in OS, PFS, and ORR versus chemotherapy in the overall population. Adding nivolumab to chemotherapy maintained clinically meaningful long-term survival benefit versus chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.
  • No Thumbnail Available
    Item
    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.
  • No Thumbnail Available
    Item
    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.