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    Home > Active Ingredient News > Digestive System Information > The control rate is as high as 93.8%, adding new force to the front line of gastric cancer immunotherapy

    The control rate is as high as 93.8%, adding new force to the front line of gastric cancer immunotherapy

    • Last Update: 2021-04-23
    • Source: Internet
    • Author: User
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    The rise of immunotherapy has injected a "cardiotonic agent" into tumor treatment, and the combination of immune + anti-angiogenesis, immune + chemotherapy and other strong combination therapies has become a new direction for tumor treatment.

    For advanced gastric cancer, immunotherapy has gradually advanced from the back line to the front line.

    Recently, a “carrelizumab combined with CAPOX program, which was led by Professor Lin Lin from Peking University Cancer Hospital, was followed by carrelizumab combined with apatinib for first-line treatment of advanced or metastatic gastroesophageal junction.
    "Adenocarcinoma" research has achieved encouraging results.

    What is the effect of this new model of first-line application of "immunization + chemotherapy + anti-angiogenesis"? The new model of gnawing "hard bone" gastric cancer is one of the common malignant tumors in my country, with a large number of patients (about 42% of gastric cancer patients in the world), late stage (a higher proportion of patients with advanced stages at the time of diagnosis), and poor survival (5 years of advanced gastric cancer survival) The rate is only 9.
    4%), and the third-line treatment rate is low, and most patients have no choice but to give up treatment.

    Adenocarcinoma of the stomach or gastroesophageal junction (G/GEJ) is the most common type of gastric cancer.

    At present, for patients with advanced G/GEJ cancer with positive expression of human epidermal growth factor receptor (HER2+) who cannot be surgically removed, a series of related clinical studies on chemotherapy combined with anti-HER2 drugs are underway.

    For HER2-negative patients, fluoropyrimidine combined with platinum-based systemic chemotherapy is still the first-line treatment option.

    However, in terms of therapeutic effects, the objective response rate is only 24.
    5-46.
    0%, and the median overall survival (OS) is 8.
    6-10.
    7 months.

    Therefore, it is urgent to explore more effective treatment options for patients with HER2-negative G/GEJ adenocarcinoma.

    In recent years, more and more evidence supports the feasibility of immunotherapy in the treatment of advanced gastric cancer.

    Nivolizumab (Drug O) and Pembrolizumab (Drug K) were initially approved in Japan and the United States for the third-line treatment of progressive G/GEJ cancer.

    In March 2020, O drug was also approved in China for the treatment of advanced G/GEJ cancers receiving ≥2 lines of systemic therapy.

    Current research is shifting to first-line applications or focusing on combination drug strategies.

    PD-1 inhibitors combined with chemotherapy, PD-1 inhibitors combined with anti-angiogenic drugs are in full swing as the first-line treatment of G/GEJ adenocarcinoma, especially the combination of PD-1 inhibitors and anti-angiogenic drugs , Which not only enhances the curative effect, but also avoids a large amount of drug toxicity, so that patients with advanced G/GEJ adenocarcinoma can achieve the maintenance or sequential treatment mode of "de-chemotherapy".

    A phase II study led by Professor Shen Lin is the first-line application of carrelizumab combined with capecitabine and oxaliplatin (CAPOX), followed by carrelizumab combined with apatinib.
    Evaluation of the efficacy and safety of the treatment of advanced or metastatic G/GEJ adenocarcinoma.

    Study Design The results of this multicenter phase II study are the results of cohort 1 released this time.

    A total of 48 patients with HER2-negative advanced or metastatic G/GEJ adenocarcinoma who had not received systemic therapy were included in the study.

    These patients received karelizumab combined with CAPOX for 4-6 cycles, and then were given karelizumab combined with apatinib sequentially.

    The main observation endpoint is the objective response rate.

    Results of the 48 patients included in the study, the objective response rate (ORR) was 58.
    3%, the disease control rate (DCR) was 93.
    8%, and the duration of response (DOR) was 5.
    7 months.

    The median overall survival (OS) was 14.
    9 months, and the median progression-free survival (PFS) was 6.
    8 months.

    The results of the study confirmed the good anti-tumor effect of the program.

    The specific data are as follows: As of February 29, 2020, there are still 4 (8.
    3%) patients who continue to receive treatment, and 44 (91.
    7%) patients stop treatment (20 patients are treated with carrelizumab combined with capecita The treatment was discontinued when the Bolin and oxaliplatin, and 24 patients in remission received follow-up carrelizumab combined with apatinib treatment).

    1).
    Among 48 patients, 1 patient (2.
    1%) achieved complete remission (CR), 27 (56.
    3%) patients achieved partial remission (PR), and 17 patients (35.
    4%) achieved stable disease (SD) ( figure 1).

    The overall objective response rate reached 58.
    3% (28/48), and the disease control rate reached 93.
    8%.

    Figure 1 Short-term efficacy evaluation of 48 patients 2).
    Overall, 43 (89.
    6%) patients had a reduction in target lesions compared to baseline (Figure 2).

    In several evaluations of target lesions, the reduction in tumor burden was maintained (Figure 3).

    The median response time was 1.
    4 months, and the median duration of response was 5.
    7 months (Figure 4).

    Figure 2 Changes in target lesions of patients from baseline Figure 3 Tumor burden assessment of 48 patients Figure 4 Tumor response duration of 28 patients (1 CR and 27 PR) 3).
    Up to now, the overall median progression-free survival is 6.
    8 Months, the median overall survival time was 14.
    9 months.

    The estimated 6, 9, and 12-month overall survival rates were 87.
    5%, 72.
    9%, and 68.
    8%, respectively (Figure 4), regardless of the level of PD-L1 expression.

    Figure 5 Interpretation of OS and PFS assessment data for the overall population: The overall good objective response rate, long-lasting response duration, and progression-free survival may translate into surprising overall survival benefits.

    This result is a significant improvement compared with chemotherapy alone (PFS, 3.
    7-5.
    6 months; OS, 8.
    6-10.
    7 months), and is also higher than the results of previous PD-1 inhibitors combined with fluoropyrimidine+platinum chemotherapy.

    This fully shows that the follow-up maintenance therapy of carrelizumab and apatinib is effective.

    The overall study results confirmed that after the first-line application of carrelizumab combined with CAPOX treatment, the sequential treatment of carrelizumab combined with apatinib has a good anti-tumor effect in the treatment of advanced or metastatic G/GEJ adenocarcinoma .

    Safety analysis In terms of safety, the most common treatment-related adverse events ≥3 grade were decreased platelet count (20.
    8%), decreased neutrophil count (18.
    8%) and hypertension (14.
    6%).

    One patient (2.
    1%) died of abnormal liver function and interstitial lung disease.

    This result is consistent with previously reported toxicity related to chemotherapy, single-dose carrelizumab and apatinib.

    Although the incidence of common hepatotoxicity and hematological toxicity increased slightly, the incidence of neurotoxicity was lower compared with the previously reported PD-1 inhibitor combined chemotherapy regimen.

    Overall, patients tolerated this combination regimen relatively well.

    Summary In HER2-negative patients with advanced or metastatic gastric/gastroesophageal junction adenocarcinoma, long-term first-line chemotherapy is less effective.

    In this study, karelizumab was added to the traditional standard chemotherapy regimen, and a sequential treatment model of karelizumab combined with apatinib was used to maximize the efficacy and reduce drug toxicity.

    The results of the study show that this combination regimen has a good anti-tumor effect as a first-line treatment for advanced or metastatic G/GEJ adenocarcinoma.
    To a certain extent, it realizes a no-chemotherapy strategy of maintenance or sequential treatment, and is based on improved efficacy.
    , The adverse reactions are well tolerated.

    Further large-sample Phase III clinical studies are very worth looking forward to.

    Pay attention to the cancer degree, download the cancer degree APP, and learn about the latest anti-cancer and anti-cancer knowledge.

    Reference 1, Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, et al.
    Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study.
    Clin Cancer Res 2019;25:515-23.
    Yasuda S, Sho M, Yamato I, Yoshiji H, Wakatsuki K, Nishiwada S, et al.
    Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo.
    Clin Exp Immunol 2013;172:500-6.
    3, Yao Y, Deng R, Liao D, Xie H, Zuo J, Jia Y, et al.
    Maintenance treatment in advanced HER2-negative gastric cancer.
    Clin Transl Oncol 2020.
    4, Bang YJ, Cho JY, Kim YH, Kim JW, Di Bartolomeo M, Ajani JA, et al.
    Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer.
    Clin Cancer Res 2017;23:5671-8.
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