ያልተለቀቁ በሽተኞች hepatocellular ካርሲኖማ (ኤች.ሲ.ሲ.)፣ የመጀመሪያው መስመር ሕክምና አማራጮች ውስን ናቸው፣ የአካባቢ መጥፋት፣ ደም ወሳጅ-ተኮር ሕክምና፣ ወይም ውጫዊ የጨረር ሕክምና ወይም ኬሞቴራፒን ጨምሮ። Sorafenib (Dogime) በአሁኑ ጊዜ ያልተመረቀ ኤች.ሲ.ሲ. ላለባቸው ታካሚዎች ብቸኛው የተፈቀደ ስርዓት ነው። የወሲብ ህክምና እቅድ. እ.ኤ.አ. በ 2017 ኤፍዲኤ ሬጎራፌኒብ (Stivarga) እና ኒቮሉማብ (ኦፕዲቮ) ከዚህ ቀደም sorafenib ለተቀበሉ ታካሚዎች ሁለተኛ መስመር የሕክምና አማራጮችን አጽድቋል። ተመራማሪዎቹ ጥምረት እንደሆነ ያምናሉ PD-L1 ማገጃ durvalumab (Imfinzi) እና CTLA-4 inhibitor tremelimumab በጣም ትክክለኛው የክሊኒካዊ ሕክምና ጥምረት ሊሆኑ ይችላሉ።
በዘፈቀደ ፣ ባለ ብዙ ማእከል ፣ ደረጃ III የሂማላያ ሙከራ (NCT03298451) ከዚህ ቀደም ያልታከሙ ፣ያልተፈቱ የኤች.ሲ.ሲ. ታካሚዎችን በአራት ቡድን ይከፈላል፡ 2 የተለያዩ ዱርቫሉማብ ከ tremelimumab ጥምር ሕክምናዎች ፣ ዱርቫልማብ ሞኖቴራፒ እና sorafenib ሞኖቴራፒ (ምስል). ተመራማሪዎቹ አጠቃላይ ድነትን (OS)ን እንደ ዋና የመጨረሻ ነጥብ እና ወደ እድገት ጊዜ፣ ከግስጋሴ-ነጻ ህልውና (PFS) እና የተጨባጭ ምላሽ መጠን (ORR) እንደ ሁለተኛ የመጨረሻ ነጥቦች ተጠቅመዋል።
ዱርቫሉባብ is a human IgG monoclonal antibody, a PD-L1 inhibitor that binds to PD-1 and CD80, allowing T cells to recognize and kill እብጠት cells without the need for antibody-dependent and cell-mediated cytotoxic activity. Tremelimumab has a similar mechanism, inhibiting CTLA-4, a cell surface receptor mainly expressed in activated T cells. The hypothesis is that inhibition of CTLA-4 will increase the activity of PD-L1 inhibitors.
In the previous phase I / II study, 40 patients with HCC evaluated the safety and tolerability of the combination. The confirmed ORR was 17.5%, of which 7 patients had partial responses (7/40 patients), and the median response time was 8 weeks. The combination is well tolerated and there is no danger signal in patients with unrespectable HCC. Subsequent research is also underway. This is achieved through the synergistic effect of the two immunotherapy drugs to achieve the ultimate anti-tumor effect. It is expected that there will be better clinical results.
