Augusti 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 varannan vecka med mFOLFOX6 (fluorouracil, leukovorin och oxaliplatin) eller mFOLFOX6 varannan vecka
Var 3:e vecka, Nivolumab 360 mg med CapeOX (capecitabin och 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 ett ytterligare effektutfallsmått hade alla randomiserade patienter (n=1,581 13.8), oavsett CPS, en statistiskt signifikant förbättring av OS, med en median OS på 95 månader (12.6 procent CI: 14.6, 11.6) i nivolumab plus kemoterapi-armen kontra 95 månader (10.9 procent KI: 12.5, 0.80) i enbart kemoterapi-armen (HR 95; 0.71 procent KI: 0.90, 0.0002; p=XNUMX).
Perifer neuropati, illamående, trötthet, diarré, kräkningar, minskad aptit, buksmärtor, förstoppning och muskuloskeletal smärta var de vanligaste biverkningarna (incidens 20%) som observerades hos patienter som fick nivolumab i kombination med fluoropyrimidin- och platina-innehållande kemoterapi.
Följande är de rekommenderade nivolumabdoserna:
Var tredje vecka, ta 360 mg i kombination med behandling som innehåller fluoropyrimidin och platina.
Varannan vecka, ta 240 mg i kombination med behandling som innehåller fluoropyrimidin och platina.
Referens : https://www.fda.gov/
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