November 2022: The Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (uHCC).
Učinkovitost so ovrednotili v HIMALAYA (NCT03298451), randomizirani (1:1:1), odprti, multicentrični študiji pri bolnikih s potrjenim uHCC, ki predhodno niso prejeli sistemskega zdravljenja HCC. Bolniki so bili randomizirani v eno od treh skupin: tremelimumab 300 mg kot enkratna enkratna intravenska (IV) infuzija plus durvalumab 1500 mg IV na isti dan, čemur je sledil durvalumab 1500 mg IV vsake 4 tedne; durvalumab 1500 mg IV vsake 4 tedne; ali sorafenib 400 mg peroralno dvakrat na dan do napredovanja bolezni ali nesprejemljive toksičnosti. Ta odobritev temelji na primerjavi 782 bolnikov, randomiziranih na tremelimumab in durvalumab na sorafenib.
The major efficacy outcome was overall survival (OS). Tremelimumab plus durvalumab demonstrated a statistically significant and clinically meaningful improvement in OS compared to sorafenib (stratified hazard ratio [HR] of 0.78 [95% CI: 0.66, 0.92], 2-sided p value = 0.0035); median OS was 16.4 months (95% CI: 14.2, 19.6) versus 13.8 months (95% CI: 12.3, 16.1). Additional efficacy outcomes included investigator-assessed progression-free survival (PFS) and overall response rate (ORR) according to RECIST v1.1. Median PFS was 3.8 months (95% CI: 3.7, 5.3) and 4.1 months (95% CI: 3.7, 5.5) for the tremelimumab plus durvalumab and sorafenib arms, respectively (stratified HR 0.90; 95% CI: 0.77, 1.05). ORR was 20.1% (95% CI: 16.3, 24.4) in the tremelimumab plus durvalumab arm and 5.1% (95% CI: 3.2, 7.8) for those treated with sorafenib.
Najpogostejši (≥20 %) neželeni učinki, ki so se pojavili pri bolnikih, so bili izpuščaj, driska, utrujenost, srbenje, mišično-skeletne bolečine in bolečine v trebuhu.
Priporočeni odmerek tremelimumaba za bolnike, ki tehtajo 30 kg ali več, je 300 mg i.v. v enkratnem odmerku v kombinaciji s 1500 mg durvalumaba v 1. ciklu/1. dan, čemur sledi 1500 mg durvalumaba intravensko vsake 4 tedne. Za tiste, ki tehtajo manj kot 30 kg, je priporočeni odmerek tremelimumaba 4 mg/kg IV kot enkratni odmerek v kombinaciji z durvalumabom 20 mg/kg IV, čemur sledi durvalumab 20 mg/kg IV vsake 4 tedne.
View full prescribing information for Imjudo.
