Dr Shitara on the 4-Year Outcomes of the CheckMate 649 Trial in GEJ Adenocarcinoma

Kohei Shitara, MD, medical oncologist, chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, discusses the 4-year outcomes of the phase 3 CheckMate 649 study (NCT02872116) of nivolumab (Opdivo) plus chemotherapy vs chemotherapy alone as a first-line treatment option for patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma.

Kohei Shitara, MD, medical oncologist, chief, Department ofGastrointestinal Oncology, National Cancer Center Hospital East, discusses the 4-year outcomes of the phase 3 CheckMate 649 study (NCT02872116) ofnivolumab (Opdivo) plus chemotherapy vs chemotherapy alone as a first-line treatment option for patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma.

Adults with previously untreated, unresectable advanced, or metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma were enrolled, irrespective ofPD-L1 expression; patients with HER2-positivity were not included. Patients were randomly assigned to receive either nivolumab plus chemotherapy, nivolumab plus ipilimumab (Yervoy), or chemotherapy alone.

The dual primary end points for the nivolumab plus chemotherapy vs chemotherapy alone arms were overall survival (OS) and progression-free survival (PFS) assessed by blinded independent central review in patients with a PD-L1 combined positive score (CPS) greater than or equal to 5.

Nivolumab plus chemotherapy represents the first PD-1 inhibitor and chemotherapy combination to exhibit long-term efficacy and acceptable safety over 4 years of follow-up in previously untreated patients with advanced gastric cancer, GEJ cancer, or esophageal adenocarcinoma. These findings are consistent with earlier assessments, further affirming this combination as the standard first-line treatment for these patients, Shitara says.

Shitara explains that the 4-year survival rate with chemotherapy plus nivolumab inpatients with a CPS of at least 5 was 17% compared with 8% with chemotherapy alone, indicating a 9% actual difference in survival rates over 4 years. This finding represents a significant benchmark in gastric cancer management, as achieving prolonged survival is typically challenging, even with chemotherapy alone, he explains. The introduction of a checkpoint inhibitor has led to durable survival, as demonstrated by this long-term follow-up, Shitara notes.

Although there were no updates on response rates, as responses are typically seen early in treatment, PFS improvements were observed. Additionally, data stratified by response at 18 weeks indicated favorable OS outcomes for patients who responded to the combination, Shitara concludes.