CheckMate -649: overall survival and progression-free survival was superior with Nivolumab plus chemotherapy versus chemotherapy in first-line treatment of gastric and esophageal cancers
CheckMate -649, a pivotal phase 3 trial evaluating Nivolumab ( Opdivo ) plus chemotherapy compared to chemotherapy alone as a first-line treatment for metastatic gastric cancer, gastroesophageal junction ( GEJ ) cancer or esophageal adenocarcinoma, met both primary endpoints of overall survival ( OS ) at a pre-specified interim analysis and progression-free survival ( PFS ) at final analysis in patients whose tumors express PD-L1 with a combined positive score ( CPS ) 5 or more.
The OS benefit was also observed in the all-randomized population.
Nivolumab is the first and only PD-1 inhibitor to demonstrate superior overall survival and progression-free survival in combination with chemotherapy when compared to chemotherapy alone in patients with gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.
The safety profiles of Nivolumab and chemotherapy in this trial are reflective of the known safety profiles of Nivolumab and chemotherapy in first-line gastric and esophageal cancers.
The results from CheckMate -649, the largest study of gastric and esophageal cancers conducted to date, indicate the potential for Nivolumab plus chemotherapy to change practice in the first-line setting and become a new standard of care for certain patients with gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.
CheckMate -649 is also evaluating the Nivolumab plus Ipilimumab combination compared to chemotherapy in patients with gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.
Checkmate -649 is a phase 3 randomized, multi-center, open-label study evaluating Nivolumab plus chemotherapy or the Nivolumab plus Ipilimumab combination compared to chemotherapy alone in patients with previously untreated, non-HER2-positive, advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.
Patients in the Nivolumab plus chemotherapy arm received Nivolumab 360 mg plus Capecitabine and Oxaliplatin ( CapeOX ) every three weeks or Nivolumab 240 mg plus 5-Fluorouracil, Leucovorin and Oxaliplatin ( FOLFOX ) every two weeks.
Patients in the Nivolumab plus Ipilimumab arm received Nivolumab 1 mg/kg plus Ipilimumab 3 mg/kg every three weeks for four cycles followed by Nivolumab 240 mg every two weeks.
Patients in the chemotherapy arm received FOLFOX or CapeOX every two or three weeks, respectively.
All patients continued treatment for two years or until disease progression, unacceptable toxicity or withdrawal of consent.
The primary endpoints of the trial are overall survival in PD-L1 positive patients with a combined positive score ( CPS ) 5 or more treated with Nivolumab plus chemotherapy and progression free survival, as assessed by BICR ( Blinded Independent Central Review ), in CPS greater than or equal to 5 patients treated with Nivolumab plus chemotherapy compared to chemotherapy alone.
Key secondary endpoints include overall survival in CPS greater than or equal to 1 and all randomized patients treated with Nivolumab plus chemotherapy as well as overall survival and time to symptom deterioration ( TTSD ) in patients treated with Nivolumab plus Ipilimumab compared to chemotherapy alone.
Gastric cancer, also known as stomach cancer, is the fifth most common cancer and the third leading cause of cancer death worldwide.
The five-year relative survival rate is 5.5% for patients diagnosed with metastatic disease in the U.S.
There are several cancers that can be classified as gastric cancer, including certain types of cancers that form in the gastroesophageal junction, the area of the digestive tract where the esophagus and stomach connect.
While gastroesophageal junction cancer has a lower prevalence than gastric cancer, it continues to rise.
First-line treatment for patients with gastric or gastroesophageal junction cancer often provides the best chance for efficacy as many patients cannot proceed to subsequent treatments in later settings due to deterioration.
Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide.
The five-year relative survival rate is 4.9% or less for patients diagnosed with metastatic disease in the U.S.
The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 15% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal adenocarcinoma occurring in North America ( 65% ).
The majority of cases are diagnosed in the advanced setting and impact a patient’s daily life, including their ability to eat and drink. ( Xagena )
Source: BMS, 2020