August 2021: For advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, the Food and Drug Administration approved nivolumab (Opdivo, Bristol-Myers Squibb Company) in conjunction with fluoropyrimidine- and platinum-containing treatment.
CHECKMATE-649 (NCT02872116) was a randomised, multicenter, open-label trial that enrolled 1,581 patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma who had previously received no treatment. The Agilent/Dako PD-L1 IHC 28-8 pharmDx test was used to calculate the combined positive score (CPS) for PD-L1. Patients were given nivolumab in combination with chemotherapy (n=789) or chemotherapy alone (n=792), with the following study treatment regimen:
Nivolumab 240 mg annenhver uke med mFOLFOX6 (fluorouracil, leucovorin og oxaliplatin) eller mFOLFOX6 annenhver uke
Hver 3. uke, Nivolumab 360 mg med CapeOX (capecitabin og oxaliplatin) eller CapeOX.
Progression-free survival (PFS) measured by blinded independent central review and overall survival were the key efficacy outcome measures in patients with PD-L1 CPS 5 (n=955) (OS). For patients with PD-L1 CPS 5, CHECKMATE-649 showed a statistically significant increase in PFS and OS. The median OS in the nivolumab + chemotherapy arm was 14.4 months (95 percent confidence interval: 13.1, 16.2) compared to 11.1 months (95 percent confidence interval: 10.0, 12.1) in the chemotherapy alone arm (HR 0.71; 95 percent confidence interval: 0.61, 0.83; p0.0001). The median PFS in the nivolumab + chemotherapy arm was 7.7 months (95 percent CI: 7.0, 9.2) versus 6.0 months (95 percent CI: 5.6, 6.9) in the chemotherapy alone arm (HR 0.68; 95 percent CI: 0.58, 0.79; p0.0001).
Som et tilleggsmål for effektutfall hadde alle randomiserte pasienter (n=1,581), uavhengig av CPS, en statistisk signifikant forbedring i OS, med en median OS på 13.8 måneder (95 prosent KI: 12.6, 14.6) i nivolumab pluss kjemoterapi-armen vs. 11.6 måneder (95 prosent KI: 10.9, 12.5) i kjemoterapi-armen alene (HR 0.80; 95 prosent KI: 0.71, 0.90; p=0.0002).
Perifer nevropati, kvalme, tretthet, diaré, oppkast, nedsatt appetitt, magesmerter, forstoppelse og muskel-skjelettsmerter var de vanligste bivirkningene (forekomst 20 %) observert hos pasienter som fikk nivolumab i kombinasjon med fluoropyrimidin- og platinaholdig kjemoterapi.
Følgende er anbefalte nivolumab-doser:
Hver tredje uke, ta 360 mg i kombinasjon med fluoropyrimidin- og platinaholdig behandling.
Ta 240 mg annenhver uke i kombinasjon med fluoropyrimidin- og platinaholdig behandling.
Henvisning : https://www.fda.gov/
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