Augusta 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 každé dva týždne s mFOLFOX6 (fluóruracil, leukovorín a oxaliplatina) alebo mFOLFOX6 každé dva týždne
Každé 3 týždne Nivolumab 360 mg s CapeOX (kapecitabín a oxaliplatina) alebo 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).
Ako ďalšie meradlo výsledkov účinnosti mali všetci randomizovaní pacienti (n = 1,581) bez ohľadu na CPS štatisticky významné zlepšenie OS s mediánom OS 13.8 mesiaca (95 percent IS: 12.6; 14.6) v ramene s nivolumabom a chemoterapiou. vs. 11.6 mesiacov (95 percent IS: 10.9, 12.5) v ramene so samotnou chemoterapiou (HR 0.80; 95 percent IS: 0.71, 0.90; p = 0.0002).
Periférna neuropatia, nauzea, únava, hnačka, vracanie, znížená chuť do jedla, bolesť brucha, zápcha a muskuloskeletálna bolesť boli najčastejšie nežiaduce reakcie (výskyt 20%) pozorované u pacientov, ktorí dostávali nivolumab v kombinácii s chemoterapiou obsahujúcou fluórpyrimidín a platinu.
Nasledujú odporúčané dávky nivolumabu:
Každé tri týždne užite 360 mg v kombinácii s liečbou obsahujúcou fluórpyrimidín a platinu.
Každé dva týždne užite 240 mg v kombinácii s liečbou obsahujúcou fluórpyrimidín a platinu.
Referencia: https://www.fda.gov/
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