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    Home > Active Ingredient News > Digestive System Information > Nature Liu Lian's team from Shandong University discovered a potential new treatment for advanced gastric cancer

    Nature Liu Lian's team from Shandong University discovered a potential new treatment for advanced gastric cancer

    • Last Update: 2023-02-03
    • Source: Internet
    • Author: User
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    Despite neoadjuvant/translational chemotherapy, cT4a/bN+ has a poor
    prognosis for gastric cancer.
    Immune checkpoint inhibitors (ICIs) and antiangiogenic drugs have shown activity in advanced gastric cancer, but their efficacy in neoadjuvant/translational settings is unclear

    On January 3, 2023, the team of Liu Lian of Shandong University published a report entitled "Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric" online in Nature Communications cancer", which conducted a single-arm phase II exploratory trial evaluating the efficacy
    of ICI (camrelizumab), antiangiogenic (apatinib), and chemotherapy (S-1±oxaliplatin) in combination with cT4a/bN+ neoadjuvanc/conversion therapy for gastric cancer.

    The results showed that the complete and major pathological response rates were 15.
    8% and 26.
    The pathological response was significantly correlated
    with microsatellite instability, PD-L1 expression and tumor mutational burden.
    In addition, multiomics revealed several presumptive biomarkers of pathological responses, including RREB1 and SSPO mutations, immune-relevant features, and peripheral T cell expansion scores
    Multiomics also demonstrated dynamic changes
    in dominant tumor subclonals, immune microenvironment, and T cell receptor repertoire during neoadjuvant immunotherapy.
    Toxicity and postoperative complications are limited
    These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapies in large randomized trials and provide candidate biomarkers

    Stomach cancer remains the leading killer worldwide, ranking fifth in incidence and fourth
    in mortality.
    Radical resection is the best option
    for treatment and prolonging survival.
    In previous MAGIC and FFCD clinical trials, perioperative chemotherapy had a higher 5-year survival rate than surgery
    The FLOT regimen further improved R0 resection rates and prolonged overall survival (OS)
    compared with the no paclitaxel regimen.
    However, cT4 patients accounted for less than 10%
    of patients in this trial.
    In a recent PRODIGY study, neoadjuvant DOS regimens (docetaxel, oxaliplatin, and S-1 [Tegafur/Gimestat/Oxonate]) and adjuvant S-1 significantly improved 3-year progression-free survival (PFS) (66.
    3 versus 59.
    8 months) for postoperative S-1 and resulted in a 10.
    4% complete pathologic response
    Although 70% of patients in this trial had cT4, a whopping 89%
    of patients with cT4a were present.
    In addition, the prognosis was lower in the cT4N+ group than in the cT4N- and cT2-3N+ groups, and there was no separate subgroup analysis
    for cT4bN+ patients.
    Recently, in phase III randomized controlled trials, immune checkpoint inhibitors (ICIs) achieved superior outcomes
    over placebo in third-line treatment of advanced gastric cancer.
    In first-line therapy, in patients with PD-L1 CPS≥5 in CheckMate 6498 and ORIENT169, combining ICI and chemotherapy prolongs OS and PFS and reduces the risk of death by 20-35%
    compared with chemotherapy alone.
    Theoretically, due to the intact immune system, sufficient neoantigens, and low tumor clonality, the neoadjuvant therapeutic environment is the best choice
    for immunotherapy.
    ICI-based neoadjuvant therapy has been successfully used for resectable non-small cell lung cancer
    In gastric cancer, especially in locally advanced gastric cancer, the role of chemotherapy remains incompletely explored
    Genomic characteristics and clonal evolution after neoadjuvant therapy (Figure from Nature Communications) Tumor angiogenesis plays an important role
    in tumor development.
    Like ICIs, antiangiogenic drugs target tumor microenvironment (TME) components rather than tumor cells and work
    synergistically with ICIs by promoting CD8+ T lymphocyte infiltration and activation.
    Ramucirumab (an anti-VEGFR2 antibody) and apatinib (a VEGFR2 tyrosine kinase inhibitor) have been shown to prolong OS and are approved for second- and third-line treatment
    of advanced gastric cancer, respectively.
    In some phase I/II studies, they have been shown to reprogram TME, reverse immunosuppression to inflammatory states, and enhance the efficacy
    of ICIs.
    Therefore, the addition of antiangiogenic drugs to ICIs plus chemotherapy regimens may enhance the efficacy
    of neoadjuvant therapy.
    In this phase II trial, the authors' data suggest that ICI-based and antiangiogenesis-based neoadjuvant/conversion therapies have good efficacy and feasibility
    in cT4a/bN+ gastric cancer, particularly in MSI-H and PD-L1-positive patients.
    How to improve its efficacy in MSS and PD-L1 negative patients needs to be further explored
    The results of the multiomics study provide a number of candidate biomarkers associated with efficacy and help understand the mechanisms
    of treatment response and drug resistance.

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