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    Home > Active Ingredient News > Digestive System Information > Dilemma and breakthrough in second-line treatment of gastric cancer: what can anti-angiogenic drugs bring us?

    Dilemma and breakthrough in second-line treatment of gastric cancer: what can anti-angiogenic drugs bring us?

    • Last Update: 2022-01-26
    • Source: Internet
    • Author: User
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    *For reference only for medical professionals
    Professor Zhang Xiaotian and Professor Chen Zhiyu, experts in the field of gastric cancer diagnosis and treatment, explained the past and present of anti-angiogenesis
    .

     China is a big country with gastric cancer.
    In 2020, the number of new cases of gastric cancer in China will reach 480,000, accounting for 43.
    9% of the world's total, ranking third in both incidence and mortality [1]

    .

    Unfortunately, about 36% of gastric cancer patients in China are diagnosed at an advanced stage, and the 5-year survival rate of these patients is only 5.
    5% [2]

    .

    Based on the REGARD study [3] and the RAINBOW study [4], in 2014, Ramucirumab was approved by the FDA for the second-line treatment of gastric cancer
    .

    Subsequently, the RAINBOW-Asia study [5] confirmed the efficacy and safety of this regimen in the Asian population
    .

    At this year's American Society of Clinical Oncology Symposium on Gastrointestinal Oncology (ASCO-GI), the results of the RAINBOW-Asia study were announced as a bridging trial of the RAINBOW study, providing strong evidence-based medical evidence for clinical practice
    .

    "Medical Community" specially invited Professor Zhang Xiaotian of Peking University Cancer Hospital and Professor Chen Zhiyu of Fudan University Cancer Hospital to explain the progress and application of anti-angiogenesis therapy in second-line treatment of gastric cancer
    .

    The treatment of advanced gastric cancer is difficult, and where is the cure? The incidence of gastric cancer in my country is more specific than many regions in the world.

    .

    Professor Zhang Xiaotian said that based on China's huge population base, the number of new gastric cancer patients is very large
    .

    This determines that there is a high unmet clinical need for gastric cancer patients in China
    .

    Due to the poor popularization of gastric cancer screening in China, about 80% of gastric cancer patients are diagnosed with advanced or locally advanced disease
    .

    These patients have late stage diagnosis and large tumor burden.
    Even if they have the opportunity to undergo radical resection, the probability of postoperative metastasis is still very high

    .

    Therefore, there are more patients in the clinic and there is a clear need for post-line treatment
    .

    At the same time, the tumor heterogeneity of gastric cancer is very strong
    .

    This tumor heterogeneity is reflected in the primary tumor and metastases, with different molecular biological characteristics
    .

    Therefore, in the process of later-line treatment, the primary tumor and metastases may appear, and even the response of metastases and metastases to treatment is different
    .

    Professor Zhang Xiaotian said that this is an urgent problem to be overcome in the era of targeted and precise treatment
    .

     In terms of gastric cancer treatment, Professor Zhang Xiaotian said that for a long time, the first-line treatment of advanced gastric cancer has been based on chemotherapy-based single-drug or combination regimens
    .

    The current efficacy of traditional first-line chemotherapy drugs has reached a plateau, and there is a huge unmet need.
    Even if it is to improve dosage forms or develop new chemotherapy drugs, it is difficult to make major breakthroughs in the short term

    .

    Therefore, to improve the treatment status of patients with advanced gastric cancer, efforts should focus on targeting and immunotherapy
    .

    In the current era of precision medicine and targeted therapy, it is hoped that specific targets can be more accurately identified in order to improve the efficacy
    .

    In a real-world study on the treatment of gastric cancer, we found that due to the limitations of clinical diagnosis and treatment and other related factors, the first- and second-line treatment regimens received by patients with advanced gastric cancer were significantly different from those recommended by guidelines.
    The effectiveness of second-line treatment needs to be improved urgently

    .

    Based on the RAINBOW study, Ramucirumab combined with chemotherapy has become the second-line standard regimen for gastric cancer.
    The American Society of Clinical Oncology (ASCO) 2014 academic annual meeting published a global phase III clinical study, which aims to treat metastatic disease.
    The efficacy of ramucirumab + paclitaxel (PTX) was compared with placebo (PL) + PTX in patients with gastric gastroesophageal junction and gastric adenocarcinoma (mGC) (RAINBOW study)

    .

    A total of 665 patients were included in the study, 330 in the ramucirumab + PTX group and 335 in the PL + PTX group
    .

    The results of the study showed that the median overall survival (mOS) of the Ramucirumab + PTX treatment group was 9.
    63 months, which was significantly improved compared with 7.
    36 months of the PL + PTX treatment group

    .

    The 6-month and 12-month survival rates of the Ramucirumab + PTX treatment group were 72% and 40%, respectively, which were also significantly higher than the PL + PTX treatment group's 57% and 30%
    .

    In addition, the progression-free survival (PFS) of the Ramucirumab + PTX treatment group and the PL + PTX treatment group were 4.
    4 months and 2.
    86 months, respectively, and the objective response rate (ORR) was 28% and 16, respectively.
    %

    .

    It is suggested that ramucirumab combined with chemotherapy is more beneficial than chemotherapy alone in second-line treatment of advanced gastric cancer
    .

     Prof.
    Zhiyu Chen said that based on the excellent performance of anti-angiogenic drugs in the REGARD study and the RAINBOW study, Ramucirumab was approved by the FDA for the second-line treatment of gastric cancer

    .

    At the same time, in the "National Comprehensive Cancer Network NCCN 2021 Guidelines for the Diagnosis and Treatment of Gastric Cancer", ramucirumab + paclitaxel is a recommended regimen for the second-line treatment of advanced gastric cancer
    .

    This undoubtedly provides the strongest evidence-based medical evidence for second-line treatment of advanced gastric cancer, and provides authoritative guidance for clinicians to use drugs
    .

     And how to exert the anti-tumor effect of anti-angiogenic drugs, Professor Chen Zhiyu introduced the relevant mechanism of anti-angiogenic drugs in detail
    .

    He said that the growth of tumors is bound to be accompanied by abnormal tumor angiogenesis, which in turn induces the production of an immunosuppressive microenvironment to help tumor cells escape immune surveillance.
    Antiangiogenic drugs are based on this

    .

    Ramucirumab, a human IgG1 monoclonal antibody, inhibits VEGFR-2 activation by specifically binding to VEGFR-2, thereby inhibiting ligand-induced endothelial cell proliferation and migration, and ultimately inhibiting tumor angiogenesis
    .

    At the same time, it can also effectively regulate the immune microenvironment by promoting the normalization of tumor blood vessels, and truly achieve the effect of "doing more with less"
    .

     RAINBOW-Asia study fills gaps in Asian population with prolonged survival At this year's American Society of Clinical Oncology Symposium on Gastrointestinal Oncology (ASCO-GI), the results of the RAINBOW-Asia study were announced as a bridging trial of the RAINBOW study
    .

    This study aims to answer the response and safety of anti-angiogenic drugs combined with chemotherapy in Asian gastric cancer population, especially Chinese gastric cancer population
    .

    A total of 440 patients from East Asia (China, Malaysia, the Philippines, and Thailand) with advanced gastric or gastroesophageal junction adenocarcinoma who had progressed after first-line chemotherapy were included in the study
    .

    Randomized 2:1 to ramucirumab + PTX or PL + PTX, with co-primary endpoints of PFS and OS
    .

    The study showed that the mPFS of patients in the Ramucirumab + PTX group was significantly prolonged compared with the placebo group (4.
    14 months vs 3.
    15 months; HR=0.
    765; p=0.
    0184), and showed that it was consistent with the global pivotal registration clinical trial.
    RAINBOW consistent mOS benefit (8.
    71 months vs 7.
    92 months; HR = 0.
    963; p = 0.
    7426)

    .

    Patients were generally well tolerated, consistent with the known safety profile of ramucirumab
    .

     Professor Zhang Xiaotian said that the RAINBOW-Asia study is a study that fills the gap of second-line anti-angiogenic targeted therapy for gastric cancer in China.
    The previous anti-angiogenic targeted therapy related research was a global study and did not include domestic patients alone

    .

    The RAINBOW-Asia study and the RAINBOW study demonstrated consistent mPFS and mOS benefits with favorable safety profiles
    .

    The positive results of the RAINBOW-Asia study are of great significance in the Asian gastric cancer population, especially the Chinese gastric cancer population
    .

     Based on the RAMBOW-Asia study, after Ramucirumab was approved for marketing, the people facing the second-line treatment of gastric cancer are often those who have progressed on PD-1 monoclonal antibody therapy
    .

    However, the combination of anti-angiogenic drugs and chemotherapy undoubtedly provides a new strategy for the second-line treatment of gastric cancer
    .

    Ramucirumab can benefit more patients with advanced gastric cancer
    .

    The application prospects are broad, and more research on anti-vascular therapy is urgently needed to reveal the future application of ramucirumab in the field of gastric cancer treatment.
    Professor Zhang Xiaotian said that ramucirumab has become the only approved drug.
    As a targeted drug for second-line treatment of advanced gastric cancer, its combination with paclitaxel has been approved for second-line treatment of gastric cancer in many countries

    .

    The success of the RAINBOW-Asia bridging study adds an important evidence-based basis for second-line treatment of advanced gastric cancer in China
    .

    Gastric cancer patients who have progressed on first-line PD-1 monoclonal antibody therapy in the future will be the main population receiving second-line anti-vascular therapy.
    Therefore, whether it is the current ramucirumab combined with chemotherapy, or combined with immune and targeted therapy, Various combination therapy modalities are worthy of further exploration for the possibility of bringing about clinical benefit

    .

    In addition, although anti-angiogenic drugs have shown good efficacy and reliable safety in clinical studies, a unique biomarker has not yet been found to accurately identify the beneficiaries of their treatment, so this will also be the subject of future research.
    important direction

    .

    At the same time, exploring the evolution of anti-angiogenic drugs from second-line treatment of gastric cancer to first-line and even neoadjuvant therapy is also a research with clinical application value
    .

    If it can play a good role in the whole treatment of gastric cancer, it is believed that ramucirumab can benefit more patients
    .

    Professor Chen Zhiyu also said that there are many studies on the combination of anti-angiogenic drugs and chemotherapy in the second-line treatment of gastric cancer, such as the ID NUMBER: 11-166 study, the NIEGA study, the ENRICH study, etc.
    , and I hope there will be more similar combination therapy models in the future.
    Good research results will benefit clinical patients

    .

    In addition, anti-angiogenesis combined immunity has also been a hot research topic in recent years.
    Several related studies are being carried out or recruited for the use of ramucirumab combined with immunotherapy for advanced gastric cancer.
    breakthrough

    .

    Expert Profile Prof.
    Zhang Xiaotian, MD, Chief Physician, Professor, Doctoral Supervisor, Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Deputy Director of the International Cooperation and Exchange Department, Peking University Cancer Hospital, Executive Deputy Director of the Department of Internal Medicine Teaching and Research Section, Chairman of the Youth Expert Committee of the Chinese Society of Clinical Oncology Chairman of the Youth Committee of the Gastric Cancer Professional Committee of the Chinese Cancer Society Reviewer of "Journal of Clinical Oncology", "Chinese Journal of Oncology", "Chinese Medical Journal", editorial expert of "Chinese Journal of Clinical Nutrition" and "People's Liberation Army Medical Journal" Medical Oncology CSCO Neuroendocrine Tumor Expert Committee Member CSCO Gastrointestinal Stromal Tumor Expert Committee Member Member of Endocrine Oncology Group (CSNET) Member of Shanghai Anti-Cancer Association Cancer Rehabilitation and Palliative Care Professional Committee and vice chairman of the Youth Committee Member of Shanghai Anti-Cancer Association Colorectal Cancer Special Committee Member of Shanghai Anti-Cancer Association Hepatobiliary and Pancreatic Tumor Comprehensive Treatment Committee Member Member of Shanghai Anti-Cancer Association Gastric Cancer Molecular Targeting and Immunotherapy Professional Committee Member of Shanghai Anti-Cancer Association Pancreatic Cancer Professional Committee Member of China Medical Promotion Association Neuroendocrine Tumor Branch (CNETS) China Medical Promotion Association Digestive Tract Tumor MDT Committee Member of the Neuroendocrine Oncology Group of the Pancreatic Disease Special Committee of the Chinese Medical Doctor Association Young Member of the MDT Special Committee of the Surgical Branch of the Chinese Medical Doctor Association References of the editorial board of the special issue of gastrointestinal cancer: [1] National Cancer Center "2020 National Cancer Report"; [2] US SEER database 2011-2017 statistics https://seer.
    cancer.
    gov/statfacts/html/stomach .
    html;[3]Charles S Fuchs , Jiri Tomasek ,Cho Jae Yong Ramucirumab monotherapy for previously treated gastric advanced or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial.
    2014 Jan 4;383(9911):31-39.
    doi: 10.
    1016/S0140-6736(13)61719-5.
    Epub 2013 Oct[4]Wilke H, Muro K, Van Cutsem E, Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW ): a double-blind, randomised phase 3 trial.
    Lancet Oncol.
    2014 Oct;15(11):1224-35.
    doi: ‍10.
    1016/S1470-2045(14)70420-6.
    Epub 2014 Sep 17.
    [5 ]Rui-Hua Xu, et al.
    RAINBOW-Asia: A randomized, multicenter, double-blind,phase 3 study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line chemotherapy with platinum and fluoropyrimidine.
    2021 ASCO GI.
    Abstract 199.
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