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    Home > Active Ingredient News > Antitumor Therapy > 2022 AWE Professor Zhou Qing interpretation and Professor Wu Yilong commented on the GEMSTONE-301 study

    2022 AWE Professor Zhou Qing interpretation and Professor Wu Yilong commented on the GEMSTONE-301 study

    • Last Update: 2022-11-01
    • Source: Internet
    • Author: User
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    At the AWE conference held online on October 22, 2022, Professor Zhou Qing of Cancer Hospital of Guangdong Provincial People's Hospital gave an in-depth interpretation of the GEMSTONE-301 study carried out in the Chinese group, and invited Professor Wu Yilong of Guangdong Provincial People's Hospital to comment on the research
    .
    Details are as follows:


    Professor Zhou Qing: In-depth interpretation of the GEMSTONE-301 study

    Professor Zhou Qing

    Cancer Hospital of Guangdong Provincial People's Hospital



    Clinical research and development background


    Stage III patients are a difficult problem in the treatment of lung cancer and require multidisciplinary team management


    About 30%-40% of patients with non-small cell lung cancer (NSCLC) in China have stage III at the initial diagnosis, which is the "critical window period" for lung cancer treatment, and radiotherapy and chemotherapy are the main treatment mode
    .
    The best strategy for stage III patients is complex and heterogeneous, and the ability to be "resectable" is highly subjective (depending on the decision of surgeon and institution), and the optimal strategy remains controversial
    .
    Professor Zhou Qing pointed out that the survival curve of stage III patients gradually stabilized in the tail, indicating that these patients have the opportunity to be cured through active treatment, about 10%~20% of patients may turn to the early stage, and even some patients may have the opportunity to undergo surgical treatment
    .
    However, some patients do not even have the opportunity to receive radiation therapy, and the treatment regimen is similar
    to that of patients with advanced disease.
    Therefore, stage III patients are a difficult problem in the treatment of lung cancer and require comprehensive treatment
    based on multidisciplinary team discussion.


    Chemoradiotherapy is the main modality, but the efficacy needs to be improved


    Concurrent chemoradiotherapy (cCRT) and sequential chemoradiotherapy (sCRT) are the main treatment methods for these patients, the former has significant OS benefit compared with the latter, but the 5-year OS rate is only 15.
    1%, and the 5-year OS rate of sCRT is 10.
    6%.

    Professor Zhou Qing pointed out that even if stage III patients can actively receive treatment, the survival rate is not ideal, and there is a lot of room for
    improvement.


    In order to further improve the efficacy of cCRT, the researchers have carried out a series of explorations, including chemotherapy induction therapy, chemotherapy consolidation therapy, increasing the dose of radiotherapy, changing the radiotherapy regimen and other previous studies on the mode of radiotherapy and chemotherapy and optimizing the radiotherapy and chemotherapy regimen, but all of them have failed
    .
    In addition, real-world studies have shown that compared with sCRT, the toxicity of cCRT is significantly increased, and the utilization rate is only 27%~55%.


    Therefore, for stage III unresectable NSCLC, improving the prognosis of patients receiving cCRT and sCRT is an unmet clinical need
    .


    Professor Zhou Qing pointed out that in 2017, the PACIFIC study swept the world like a "tsunami", opening a new model of stage III unresectable lung cancer, and confirming for the first time that cCRT sequential immune consolidation therapy can bring obvious survival benefits
    。 However, the following questions remain worth further exploring: whether patients with different baseline characteristics benefit (more patients with stage IIIA, non-squamous cell carcinoma, and PS 0 are included in the PACIFIC study), whether Chinese patients benefit (the PACIFIC study has fewer Asian patients, and it is unclear whether the results can be extrapolated to Chinese patients), reproducibility (only the PACIFIC study confirmed the benefit of immune consolidation therapy after cCRT), and the benefit of sequential immune consolidation therapy with sCRT



    Clinical research and development ideas and results


    Suglilimab is a fully human, full-length IgG4 targeted PD-L1 monoclonal antibody, unlike other PD-L1 monoclonal antibodies, suglilimab retains antibody-dependent cell-mediated phagocytosis (ADCP) and has a dual anti-tumor mechanism: it can simultaneously induce T cells and macrophages to kill tumor cells
    .
    First, by blocking the PD-1/PD-L1 signaling pathway, the anti-tumor effect
    of T cells is enhanced.
    Second, the antibody Fc segment binds to the macrophage surface FcγR to activate the ADCP effect
    .


    The GEMSTONE-301 study was tailored for Chinese patients


    GEMSTONE-301 is designed to explore the efficacy
    of suglilimab for consolidation therapy in progression-free phase III patients following chemoradiotherapy.
    At the same time, the efficacy of immunoconsolidation therapy after receiving cCRT or sCRT was explored, and stage III unresectable Chinese patients were included, and drivers positive patients
    were excluded.
    Professor Zhou Qing pointed out that the study appropriately relaxed the inclusion criteria for patients with minor injuries to liver and kidney function, and also included patients with grade 1 radiation pneumonia in the study, which is closer to the real clinical situation
    .


    Latest results


    Baseline characteristics showed that the population enrolled in the GEMSTONE-301 study was more "refractory", with more stage IIIB/IIIC and more
    squamous cell carcinoma.


    Figure baseline characteristics


    On this basis, the study still achieved good results and reached the primary endpoint
    .
    As of 1 March 2022, the median follow-up was 27.
    1 months and 23.
    5 months in the Sougley and comfort groups, respectively, and the median PFS assessed by BICR was 10.
    5 months and 6.
    2 months, respectively (HR=0.
    65).

    Suglilimab significantly reduces the risk of disease progression by 35%
    in the general population.
    The median PFS in the sCRT subgroup was 8.
    1 versus 4.
    1 months (HR=0.
    57), and the median PFS in the cCRT subgroup was 15.
    7 vs 8.
    3 months (HR=0.
    71),
    respectively.
    Professor Zhou Qing pointed out that the results of the concurrent chemoradiotherapy group were similar to the PACIFIC study, and the results of the general population were greatly
    affected by the population in the "sequential chemoradiotherapy" group.


    Figure research results


    The duration of response was 24.
    1 months and 6.
    9 months
    in the suglilimab and placebo groups, respectively.
    There is no doubt that patients who can benefit from immunotherapy will have long-lasting
    results.


    Professor Zhou Qing pointed out that as of now, the only immature data is OS results, and further OS analysis results
    are expected to be released next year.
    In terms of safety, the incidence of adverse events in both groups was similar, which shows that immunotherapy will produce related adverse events, such as changes in thyroid function
    .
    For pneumonia, which is of greater concern to clinicians, the incidence was similar
    in both groups.


    Based on this, suglilimab, as a consolidation therapy after concurrent or sequential chemoradiotherapy, has been included in the guidelines and expert consensus, including the 2022 version of the guidelines for the diagnosis and treatment of non-small cell lung cancer (CSCO) (level III recommendation), the clinical application guidelines for immune checkpoint inhibitors (CSCO) 2022 (class IA evidence), and the expert consensus on the diagnosis and treatment of stage III non-small cell lung cancer 2022 (degree of evidence: medium; Recommended intensity: medium).

    Reviews of big coffee - Professor Wu Yilong: One of the most important clinical studies in five years

    Prof.
    Yilong Wu

    Guangdong Provincial People's Hospital


    The GEMSTONE-301 study is a clinical trial
    to explore the efficacy of immune consolidation therapy in patients with stage III NSCLC who achieve stable (SD) or partial remission (PR) after concurrent or sequential chemoradiotherapy.
    Professor Wu Yilong believes that the GEMSTONE-301 study is one of the most important clinical studies in the field of phase III unresectable NSCLC in the past five years, because the study takes into account a high proportion (40%-50%) of patients who have been previously ignored by PACIFIC studies
    .
    Data from the United States, the United Kingdom and China all show that 40%-60% of patients do not receive concurrent chemoradiotherapy, so this proportion of patients should not be ignored, which is the significance of the GEMSTONE-301 study and why it is called one of
    the most important clinical studies in five years.


    For the GEMSTONE-301 study, we should focus on two points: first, whether the results of PACIFIC are relatively consistent
    with the concurrent chemoradiotherapy group.
    After a long enough follow-up, results published at the WCLC this year showed that the median PFS of patients in the concurrent chemoradiotherapy group reached 15.
    7 months, which is very close to
    the PACIFIC study data.
    THEREFORE, THE GEMSTONE-301 DATA FURTHER CONFIRM PACIFIC'S FINDINGS
    .
    This suggests the superiority of immunoconsolidation therapy followed by concurrent chemoradiotherapy
    .


    Second, whether patients receiving sequential chemoradiation can also benefit from immunotherapy
    .
    GEMSTONE-301 clearly suggests that the benefit of consolidation immunotherapy after sequential chemoradiotherapy even exceeds that of concurrent chemoradiotherapy, with an HR value of 0.
    57, reducing the risk of disease recurrence by nearly 50%, which is the second huge contribution
    .
    Confirmed by GEMSTONE-301, in clinical practice, for unresectable patients, whether after simultaneous or sequential chemoradiotherapy, suglilimab can be used as a consolidation therapy, which has been approved by CDE in China, has also been written into various guidelines, and is also the first study
    in the world to remind us that suglilimab can be used as a conventional treatment after sequential chemoradiotherapy.


    However, it should be emphasized that: First, sequential chemoradiotherapy cannot be given to all patients because the HR of sequential chemoradiotherapy is better than concurrent chemoradiotherapy, which is a misunderstanding
    .
    Overall, patients with concurrent chemoradiotherapy lived longer, surviving better than sequential chemoradiotherapy
    in both the experimental and placebo groups.
    Therefore, concurrent chemoradiotherapy should be preferred in stage III unresectable patients, but sequential chemoradiotherapy may be used in patients who cannot receive concurrent chemoradiotherapy
    .


    Second, GEMSTONE-301 was selected for advanced stages, with only 25.
    4% of stage IIIA patients, compared with about 60% of PACIFIC stage IIIA patients
    .
    After including patients with advanced disease, GEMSTONE-301 also demonstrated the reliability
    of this model.


    Third, in terms of safety, the safety of sequential chemoradiotherapy is better than that of concurrent chemoradiotherapy, based on this, in clinical practice, for patients with better physical condition and relatively young, sequential suglilimab or duvalumab should be treated with concurrent chemoradiotherapy as much as possible, but for patients with poor physical condition, or older age, or other reasons need to receive sequential chemoradiotherapy, we can only choose suglilimab as maintenance therapy
    .

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