#Checkmate 577 protocol trial

In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell tumor immune surveillance. Binding of PD-L1 and PD-L2 to the PD-1 receptor inhibits T-cell proliferation and cytokine production. Nivolumab is a human immunoglobulin G4 monoclonal antibody that binds the PD-1 receptor on T cells and blocks its interaction with the ligands PD-L1 and PD-L2, thereby releasing PD-1 pathway–mediated inhibition of immune response. The benefit of nivolumab was observed regardless of tumor PD-L1 expression or histology. Median disease-free survival was 22.4 months (95% confidence interval = 16.6–34.0 months) in the nivolumab group vs 11.0 months (95% CI = 8.3–14.3 months) in the placebo group (hazard ratio = 0.69, 95% CI = 0.56–0.85, P =. The main efficacy outcome measure was disease-free survival, defined as the time from date of randomization to the time of investigator-assessed first recurrence (local, regional, or distant) or death from any cause prior to subsequent anticancer therapy. PD-L1 status was positive (≥ 1% expression) in 16%, negative in 72%, and indeterminate or could not be evaluated in 12%. Histology was adenocarcinoma in 71% and squamous cell carcinoma in 29%. Eastern Cooperative Oncology Group performance status was 0 (58%) or 1 in all patients disease stage was II in 35% and III in 65% 60% had esophageal cancer and 40% had GEJ cancer and 58% had pathologic positive lymph node status. Nivolumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, and nephritis and renal dysfunction infusion-related reactions complications of allogeneic hematopoietic stem cell transplantation and embryofetal toxicity.Īmong all patients, median age was 62 years (36% ≥ 65 years) 85% were male 82% were White, 15% were Asian, and 1.1% were Black.

#Checkmate 577 protocol trial

The trial excluded patients who did not receive concurrent chemoradiotherapy prior to surgery and those who had stage IV resectable disease, autoimmune disease, or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications. 2,3 In the trial, 794 patients with completely resected esophageal or GEJ cancer who had residual pathologic disease following neoadjuvant concurrent chemoradiotherapy were randomly assigned 2:1 to receive nivolumab (n = 532) at 240 mg or placebo (n = 262) every 2 weeks for 16 weeks, followed by nivolumab at 480 mg or placebo every 4 weeks, beginning at week 17 for up to 1 year of treatment. 1,2Īpproval was based on findings from the double-blind, phase III CheckMate 577 trial ( identifier NCT02743494).

2013: Stahl et al.On May 20, 2021, nivolumab was approved for adjuvant treatment of patients with completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease after neoadjuvant chemoradiotherapy.

Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline PubMed Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.

8.7.3 Regimen variant #3, 100 mg/m 2, 3 out of 4 weeks.

8.7.2 Regimen variant #2, 80 mg/m 2, 3 out of 4 weeks.

8.5.2 Regimen variant #2, 4 out of 6 weeks.

8.5.1 Regimen variant #1, 14-day cycles.8.2.1 Regimen variant #1, 75 mg/m 2, indefinite.

8 Metastatic or locally advanced disease, subsequent lines of therapy.

7.15.2.3 Dose and schedule modifications.

7.3 Cisplatin & Fluorouracil (CF) & Pembrolizumab.

7 Metastatic or locally advanced disease, first-line.

5 Consolidation after definitive therapy.

3.14.2 Regimen variant #2, 50.4 Gy, weekly oxaliplatin.

3.14.1 Regimen variant #1, 50.4 Gy, bi-weekly oxaliplatin.

3.10 Cisplatin & Fluorouracil (CF) & RT.

3.8.2 Regimen variant #2, 6 weeks of chemotherapy.3.8.1 Regimen variant #1, 5 weeks of chemotherapy.3.4 Capecitabine, Docetaxel, Oxaliplatin, RT.3.1 Capecitabine, Carboplatin, Paclitaxel, RT.