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    Home > Active Ingredient News > Digestive System Information > Rewrite clinical practice: disease-free survival is doubled, and immune adjuvant therapy for esophageal cancer will become a new standard!

    Rewrite clinical practice: disease-free survival is doubled, and immune adjuvant therapy for esophageal cancer will become a new standard!

    • Last Update: 2021-04-19
    • Source: Internet
    • Author: User
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    Esophageal cancer is one of the leading causes of cancer deaths worldwide.

    Esophageal squamous cell carcinoma is the most common histological type in high-incidence areas such as East Asia, and esophageal adenocarcinoma is the main histological type in Western countries.

    There is currently no standard adjuvant treatment plan for patients with esophageal cancer or gastroesophageal junction adenocarcinoma with a high risk of recurrence after neoadjuvant chemotherapy and surgery.

    On April 1, the "New England Journal of Medicine" published the results of Phase III CheckMate577 [1], and published a concurrent review by Dr.
    David H.
    Ilson of the Memorial Sloan-Kettering Cancer Center [2].

    Early exploration of resectable esophageal cancer A 1980 study suggested that the treatment of esophageal squamous cell carcinoma was a daunting challenge: only 58% of patients underwent surgical exploration, and only 39% of patients received surgical resection.

    Among them, 30% of patients died during or shortly after the operation, the 2-year survival rate was 9%, and the 5-year survival rate was 4%.

    This sobering article laid the foundation for the follow-up study of preoperative chemotherapy or preoperative radiochemotherapy.

    The RTOG 85-01 study established the standard treatment model for esophageal cancer with radiotherapy and chemotherapy, or sequential surgery.

    The chemotherapy (carboplatin + paclitaxel) + short-term radiotherapy adopted in the CROSS study is currently the common treatment in clinical practice in the United States.

    Patients who achieve complete pathological remission after radiotherapy and chemotherapy have a longer survival time.

    However, most patients, especially those with positive lymph nodes, will relapse one year after surgery.

    There is still controversy about whether chemotherapy should be given priority to esophageal cancer before surgery or radiotherapy and chemotherapy.
    At present, there are many studies that are still conducting related explorations: ESOPEC study, Neo-AEGIS study, TOPGEAR study, CRITICS-II study.

    Research progress of radiotherapy and chemotherapy + immunotherapy The research progress of combined therapy for esophageal cancer is still relatively slow.

    Studies have shown that the addition of bevacizumab, trastuzumab, and cetuximab to chemotherapy or radiotherapy did not prolong the survival of patients.

    Neither in esophageal squamous cell carcinoma or esophageal adenocarcinoma, there are no targetable driver genes.

    The immune checkpoint inhibitor seems to have anti-tumor activity in both types of esophageal cancer, but its benefit is limited to patients with PD-L1 expression.

    Nivolizumab (regardless of PD-L1 status) and pembrolizumab are currently approved for second-line and above treatment of esophageal cancer resistant to conventional chemotherapy.

    The results of immunotherapy + chemotherapy for the first-line treatment of esophageal cancer have been mixed.

    The CheckMate577 study was published online on April 1 in the New England Journal of Medicine.
    On April 1, the results of the CheckMate577 study were published online in the New England Journal of Medicine.

    This is a randomized, double-blind, placebo-controlled, global Phase III clinical study to evaluate the efficacy of nivolumab for adjuvant treatment of esophageal cancer or gastroesophageal junction adenocarcinoma.

    The study included patients with stage II/III R0 resection and pathological residual who had previously received neoadjuvant chemoradiation and were randomly assigned to receive nivolumab (240 mg, Q2W, 16 weeks) and then nivolumab ( 480mg, Q4W), or placebo treatment.

    Adjuvant therapy lasts up to 1 year, and the primary endpoint is disease-free survival (DFS).

    The results showed that at a median follow-up of 24.
    4 months, 532 patients and 262 patients were treated with nivolumab and placebo, and the median DFS was 22.
    4 months and 11 months (HR=0.
    69, P< 0.
    001).

    The DFS results of the total population were based on the DFS results of histological classification.
    Moreover, the benefit of the nivolumab group was observed in the predetermined subgroups.

    Compared with adenocarcinoma (HR=0.
    75), esophageal squamous cell carcinoma benefited more (HR=0.
    61); both lymph node-negative (HR=0.
    74) and lymph node-positive (HR=0.
    67) patients benefited; different pathologies after neoadjuvant treatment Staged patients benefited (ypT0[HR=0.
    35], ypT1 or ypT2[HR=0.
    60], ypT3 or ypT4[HR=0.
    84]); HER2-positive (HR=0.
    78) and HER2-negative patients (HR=0.
    69) Benefit; PD-L1 negative (HR=0.
    73) and PD-L1 positive (HR=0.
    75) patients benefit; compared with patients with gastroesophageal junction adenocarcinoma (HR=0.
    87), patients with esophageal cancer (HR= 00.
    61) The benefits are more obvious.

     In the subgroup analysis, no new adverse events were observed, and only 9% of patients discontinued nivolumab due to treatment-related adverse events.

    Most importantly, the 1-year neoadjuvant treatment with nivolumab has no adverse effect on the quality of life reported by patients.

    Dr.
    David H.
    Ilson of CheckMate577, who changed clinical practice, believes that CheckMate577 is a study that changes clinical practice in the field of esophageal cancer.
    The overall survival (OS) data is not yet mature, but doubling the median DFS is likely to translate into OS benefits.
    .

    This research is the first real progress in the field of adjuvant treatment of esophageal cancer in recent years, and it will become a new standard of treatment.

    However, most patients will not benefit from adjuvant nivolumab treatment.
    More biomarkers, including continuous circulating tumor DNA (ctDNA) after surgery, should be explored to better identify high-risk groups and potentially acceptable Patients on immune adjuvant therapy.

    Chemoradiation and post-operative adjuvant therapy with nivolumab has achieved positive results.
    However, whether immunotherapy will improve the outcome of patients with chemotherapy but not surgery is still being explored (KEYNOTE-975).
    Perioperative chemotherapy but no radiotherapy It is also being explored whether there will be any benefit to patients receiving immunotherapy (KEYNOTE-585).

    For patients with esophageal cancer who have received chemotherapy, radiotherapy and surgery, it has been a long time to improve the survival rate again.
    The results of the CheckMate 577 study provide new treatment options for such patients.

    References: [1] Kelly RJ, Ajani JA, Kuzdzal J, et al.
    CheckMate 577 Investigators.
    Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.
    N Engl J Med.
    2021 Apr 1;384(13):1191-1203.
    doi: 10.
    1056/NEJMoa2032125.
    PMID: 33789008.
    [2] Ilson DH.
    Adjuvant Nivolumab in Esophageal Cancer-A New Standard of Care.
    N Engl J Med.
    2021 Apr 1;384(13):1269-1271.
    doi: 10.
    1056/ NEJMe2101983.
    PMID: 33789017.
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