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    Home > Active Ingredient News > Antitumor Therapy > 2021 CSCO looks forward to the front line of China’s gastric cancer advancing into the immune era, and the classics return to the "stomach"

    2021 CSCO looks forward to the front line of China’s gastric cancer advancing into the immune era, and the classics return to the "stomach"

    • Last Update: 2021-09-30
    • Source: Internet
    • Author: User
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    At the end of August, based on the landmark Phase III clinical study CheckMate-649, the National Medical Products Administration (NMPA) approved Odivo® (Nivolumab injection) combined with fluorouracil and platinum-based chemotherapy for first-line treatment Patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma
    .

    A PD-1 inhibitor-based immune combination therapy has finally been approved as a first-line indication for gastric cancer in China for the first time! While the first-line treatment of gastric cancer in China has officially entered the age of immunity, we are also about to usher in the 2021 CSCO annual meeting
    .

    The conference will be held online.
    The main researcher of CheckMate-649 in China and the deputy dean of Peking University Cancer Hospital, Professor Lin Shen, is expected to be on the conference line at 11:45-12:00 on September 27th.
    Conference Room 3 provides an in-depth inventory and interpretation of the Chinese population data of this classic study in the form of an oral report, and shares the significance and far-reaching impact of first-line immunotherapy on the diagnosis and treatment of gastric cancer in China.
    Stay tuned! "Stomach" is the first line, CheckMate-649 study OS/PFS double end point is positive! Patients with advanced gastric cancer often suffer from weight loss and malnutrition, resulting in decreased tolerance of treatment.
    Therefore, first-line treatment is the best opportunity for them to achieve better results
    .

    In the past, chemotherapy was the standard first-line treatment for unresectable advanced gastric cancer, but the chemotherapy of gastric cancer has gradually encountered a bottleneck, and the median overall survival (OS) of patients cannot exceed 1 year 1
    .

    In the past 10 years, the treatment of advanced gastric cancer has progressed very slowly.
    Previously, only trastuzumab combined with chemotherapy has achieved OS benefit in HER2-positive patients, but the proportion of HER2-positive gastric cancer in Chinese patients is only 12-13 %2
    .

    In this context, CheckMate-649 Study 3 is the first major breakthrough in the field of first-line treatment of gastric cancer in the past ten years, and also the first success of immunotherapy in this field-nivolumab combined with chemotherapy is better than chemotherapy alone The dual benefit of overall survival (OS) and progression-free survival (PFS) is achieved
    .

    Study design: The largest scale and a large population in China CheckMate -649 is currently the largest prospective phase III study in the field of upper gastrointestinal tumors.
    A total of 175 research centers in 29 countries and regions participated, and more than 2000 patients were enrolled.
    The large sample population includes various gastric cancer types and molecular classifications from the East and the West, reducing the impact of the high heterogeneity of gastric cancer on the research results
    .

    Considering that China is a country with a high incidence of gastric cancer, the CheckMate-649 study included 208 Chinese patients with gastric cancer and gastroesophageal junction cancer, who were randomly assigned to the nivolumab combined chemotherapy group or chemotherapy alone group, and their proportion in all countries In the first place
    .

    Global population results: Nivolumab combined with chemotherapy has a significant survival benefit, and is not limited by PD-L1 expression levels.
    At the 2020 ESMO annual meeting, it was announced in the CheckMate-649 study that the nivolumab combined with chemotherapy group compared to chemotherapy alone Group of global population data
    .

    Regarding OS, regardless of the expression of PD-L1 CPS in patients, nivolumab combined with chemotherapy as first-line treatment can bring both statistically and clinically significant improvements in OS for patients with advanced gastric cancer: in PD-L1 CPS ≥ 5 Among patients, patients with CPS ≥ 1, and all randomized populations, the median OS of the immune+chemotherapy group was 14.
    4, 14.
    0, and 13.
    8 months (the chemotherapy group was 11.
    1, 11.
    3, and 11.
    6 months, respectively), and the risk of death decreased by 29 %, 23%, 20%
    .

    In terms of PFS, in patients with PD-L1 CPS ≥ 5, the median PFS of the immune-combined chemotherapy group was significantly prolonged, reducing the risk of disease progression or death by 32% (median PFS: 7.
    7 vs 6.
    0 months; HR 0.
    68); PD-L1 CPS ≥ 1 and in all randomized populations, immune combination chemotherapy compared with chemotherapy alone also showed the trend of PFS benefit
    .

    The Chinese subgroup: The disease progression and mortality risk of patients with nivolumab combined with chemotherapy have been significantly reduced, and the benefit trend is better.
    At the 2021 AACR annual meeting, the Chinese subgroup data preset in the CheckMate-649 study were further announced, which is also the first And the only one to date from the Chinese subgroup of the Phase III study of first-line immunotherapy for gastric cancer
    .

    A total of 208 Chinese patients were included in this analysis.
    Compared with the global population, the benefits of Chinese patients receiving nivolumab combined with chemotherapy are consistent
    .

    In terms of OS, the median OS value of the entire population has been greatly extended, and the reduction in mortality risk is even greater globally (Figure 1): In all randomized populations, the median OS of the two groups was 14.
    3 vs 10.
    3 months, respectively, and the risk of death was reduced.
    In patients with PD-L1 CPS ≥ 1, the median OS of the two groups was 14.
    3 vs 9.
    9 months, the risk of death was reduced by 38%, and the OS increased by 4.
    4 months; Among patients with PD-L1 CPS ≥ 5, the median OS of the two groups was 15.
    5 vs 9.
    6 months, respectively, the risk of death was reduced by 46%, and the OS increased by nearly 6 months
    .

    In terms of PFS, all populations also achieved clinically significant PFS improvement, and the risk of disease progression or death was reduced by 43% (Figure 1); especially in patients with PD-L1 CPS ≥ 5, nivolumab combined with chemotherapy The median PFS was nearly twice that of chemotherapy alone, which reduced the risk of disease progression or death by 48% (median PFS: 8.
    5 vs 4.
    3 months; HR 0.
    52)
    .

    Figure 1: In terms of OS and PFS (Chinese subgroup) remission of all random populations, the objective remission rate of Chinese patients receiving immune + chemotherapy (ORR, 59% vs.
    41%, of which 68% vs.
    48 for CPS ≥ 5 population) %) and median duration of response (DoR, 12.
    2 months vs.
    5.
    6 months) compared with chemotherapy, clinically significant improvements were also observed
    .

    In summary, the results of the CheckMate-649 study show that, regardless of the global population or the Chinese subgroup, regardless of the patient's PD-L1 expression level, nivolumab combined with chemotherapy has brought double improvements in OS and PFS, and has clinical significance.
    Multiple benefits, and the trend of benefit for Chinese patients is more significant
    .

    Relying on the results of CheckMate-649, both CSCO in China and NCCN in the United States have included nivolumab combined chemotherapy regimens in the new version of the gastric cancer diagnosis and treatment guidelines, unanimously recommending it for the first-line treatment of inoperable advanced or metastatic gastric cancer
    .

    "Full coverage" of the upper gastrointestinal tract, creating a new benchmark for treatment.
    Upper gastrointestinal tumors represented by gastric cancer and esophageal cancer are China's high-incidence "characteristic" cancer types, and the progress of innovative treatments is much slower than other major solid tumors
    .

    Fortunately, in recent years, the progress of nivolumab-based therapy in the upper gastrointestinal tract has ushered in a "blowout".
    In addition to CheckMate -649, a number of heavyweight Phase III research results have been harvested in recent years, which is expected to lead This field of refractory diseases as a whole has entered the age of immunity
    .

    In the field of esophageal cancer, which is also a high incidence of cancer in the Chinese population, CheckMate-648 Study 4 evaluated the efficacy and safety of nivolumab-based combination therapy in the first-line treatment of advanced esophageal squamous cell carcinoma
    .

    The results show that two combination therapies based on nivoliumab (nivolumab + chemotherapy, nivoliumab + ipilimumab) for the first-line treatment of advanced esophageal squamous cell carcinoma can be obtained compared to chemotherapy alone Significant OS benefit, regardless of the patient's PD-L1 expression level (Figure 2); this is the first time that the "no chemotherapy" regimen has achieved a breakthrough in the first-line treatment phase III study of esophageal cancer
    .

    Based on the success of the CheckMate-649 and CheckMate-648 studies, nivolumab became the first and currently the only confirmed first-line treatment of various histological types (squamous cell carcinoma, adenocarcinoma) and tumor sites (stomach, esophagus, Tumors of the upper gastrointestinal tract at the gastroesophageal junction can all bring significant OS benefit PD-1 inhibitors
    .

    Figure 2: OS (O+chemotherapy vs.
    chemotherapy; O+Y vs.
    chemotherapy) of all random populations in the CheckMate-648 study and in the treatment of earlier gastrointestinal cancers, such as the perioperative treatment of early/operable gastrointestinal tumors , Phase III study CheckMate -5775 evaluated the efficacy and safety of nivolumab as adjuvant therapy in patients with esophageal cancer and gastroesophageal junction cancer with residual pathology after sequential neoadjuvant chemoradiation surgery
    .

    The results showed that compared with the placebo group, the disease-free survival (DFS) of the adjuvant nivolumab group was doubled (Figure 3), and the risk of disease recurrence or death was reduced by 31% (median DFS: 22.
    4) vs 11.
    0 months; HR 0.
    69)
    .

    This study is the first to observe the value of immunotherapy for adjuvant therapy in such patients
    .

    In May of this year, nivolumab was approved by the FDA, becoming the world's first adjuvant immunotherapy for esophageal cancer
    .

    Figure 3: DFS of patients in the CheckMate-577 study.
    In summary, the Phase III research results represented by CheckMate-649/648/577 have achieved a leap in clinical benefit for patients with upper gastrointestinal cancer and opened up for future explorations.
    A whole new situation
    .

    As the first-line treatment of advanced gastric cancer in China officially enters the age of immunity, we also look forward to the interpretation of Professor Shen Lin at this year’s CSCO annual meeting to bring more useful guidance and inspiration to Chinese clinicians, and further promote China’s digestion.
    The overall development of cancer diagnosis and treatment
    .

    References: 1.
    Bang YJ, Van Cutsem E, Feyereislova A, et al.
    Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open- label, randomised controlled trial[J].
    The Lancet, 2010, 376(9742): 687-697.
    2.
    Kohei Shitara, Eishi Baba, Kazumasa Fujitani ,et al.
    Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2‑positive gastric cancer[J].
    Gastric Cancer.
    2021; 24(4): 780–789.
    3.
    Yelena Y Janjigian, Kohei Shitara, Markus Moehler,et al.
    First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastrooesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial[J].
    Lancet.
    2021 Jul 3;398(10294):27-40.
    4.
    Ian Chau,Yui chiro Doki,Jaffer A.
    Ajani,et al.
    Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study[J].
    Journal of Clinical Oncology 39(18_suppl):LBA4001-LBA4001.
    5.
    Ronan J.
    Kelly, Jaffer A.
    Ajani, Jaroslaw Kuzdzal, et al.
    Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer[ J].
    N Engl J Med 2021; 384:1191-1203.
    et al.
    Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer[J].
    N Engl J Med 2021; 384:1191-1203.
    et al.
    Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer[J].
    N Engl J Med 2021; 384:1191-1203.
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