the Food and Drug Administration approved nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and oesophageal adenocarcinoma.
Efficacy was evaluated in CHECKMATE-649, a randomised, multicentre, open-label trial that enrolled 1,581 patients with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, or oesophageal adenocarcinoma.
PD-L1 combined positive score (CPS) was determined centrally using the Agilent/Dako PD-L1 IHC 28-8 pharmDx test. Patients received nivolumab in combination with chemotherapy (n=789) or chemotherapy alone (n=792); study treatment was administered as follows:
Nivolumab 240 mg with mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) every 2 weeks, or mFOLFOX6 every 2 weeks.
Nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks, or CapeOX every 3 weeks.
The main efficacy outcome measures, assessed in patients with PD-L1 CPS ≥5 (n=955), were progression-free survival (PFS) assessed by blinded independent central review and overall survival (OS).
CHECKMATE-649 demonstrated a statistically significant improvement in PFS and OS for patients with PD-L1 CPS ≥5. Median OS was 14.4 months (95% CI: 13.1, 16.2) in the nivolumab plus chemotherapy arm vs. 11.1 months (95% CI: 10.0, 12.1) in the chemotherapy alone arm (HR 0.71; 95% CI: 0.61, 0.83; p<0.0001). Median PFS was 7.7 months (95% CI: 7.0, 9.2) in the nivolumab plus chemotherapy arm versus 6.0 months (95% CI: 5.6, 6.9) in the chemotherapy alone arm (HR 0.68; 95% CI: 0.58, 0.79; p<0.0001).
As an additional efficacy outcome measure, a statistically significant improvement in OS was also demonstrated for all randomised patients (n=1,581) irrespective of CPS, with a median OS of 13.8 months (95% CI: 12.6, 14.6) in the nivolumab plus chemotherapy arm vs. 11.6 months (95% CI: 10.9, 12.5) in the chemotherapy alone arm (HR 0.80; 95% CI: 0.71, 0.90; p=0.0002).
The most common adverse reactions (incidence ≥20%) observed in patients receiving nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy were peripheral neuropathy, nausea, fatigue, diarrhoea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.
The recommended nivolumab dosages are:
360 mg every 3 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks.
240 mg every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks.
View full prescribing information for nivolumab.
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