Immunotherapy iyo daaweynta kansarka
In recent years, the popularity of immunotherapy in the field of oncology is continuing to rise. Lancet Oncol published the preliminary results of the Keynote-012 study evaluating the efficacy of the PD-L1 inhibitor pembrolizumab in patients with advanced gastric cancer on May 3, which attracted a lot of attention. Professor Elizabeth C Smyth of the Royal Marsden Hospital in England interpreted the study, which can bring us some thoughts and inspirations.
Saadaalinta kansarka caloosha ee horumarsan waa mid liita, in ka yar 10-15% bukaanada metastatic ayaa noolaan kara in ka badan 2 sano. Trastuzumab iyo ramoluzumab oo loogu talagalay daaweynta safka labaad ee bukaanada kansarka caloosha ku dhaca ee HER2-positive waxay waxyar hagaajin karaan badbaadada guud. Sababtoo ah waxaa jira tusaalooyin badan oo ku saabsan fashilka dawooyinka daweynta ee ku saabsan qaybta kansarka caloosha, waxay umuuqataa in daawooyinkan ay gaareen guul yar. Xaaladdan adag ee hadda jirta ee daaweynta kansarka caloosha ee horumarsan, Daraasadda Muhiimka ah-012 ee ay sameeyeen Professor Kei Muro iyo asxaabtiisuba waxay markii hore muujiyeen natiijooyin wanaagsan, oo tilmaamaysa in ka hortagayaasha PD-L1 ay leeyihiin qiime daaweyn kara kansarka caloosha ee horumarsan.
Natiijooyinka ka soo baxay Daraasadda aaladda-012 waa wax lala yaabo
Daraasadda Keynote-012, bukaanada PD-L1-togan ee qaba kansarka gaaska ee horumarsan waxay heleen anti-PD-1 antibody pembrolizumab ilaa cudurka uu ka sii socdo ama dhacdooyin aan loo dulqaadan karin. Daraasadu waxay baartey wadarta bukaanada 162 ee qaba kansarka caloosha ee horumarsan, kuwaas oo 65 (40%) ay ku fiicnaadeen muujinta PD-L1, ugu dambeyntiina 39 (24%) bukaanno ayaa lagu qoray daraasaddan caalamiga ah ee Wajiga 1B. Si xiiso leh, 17 ka mid ah 32ka bukaan (53%) waxay la kulmeen dib-u-dhac buro; 8 ka mid ah 36 (22%) bukaanada leh waxtarka laqiimeyn karo waxay xaqiijiyeen in qeyb ahaan laga soo saaray. Qiyaasta cafiskaan waxay la jaanqaadaysaa natiijooyinka tijaabooyinka difaaca jirka ee kansarrada kale, oo leh jawaab celcelis dhexdhexaad ah oo 40 toddobaad ah, iyo 4 ka mid ah 36 bukaan (11%) leh cudur ka dhaafid ah ma muujin horumarka cudurka illaa waqtiga warbixinta. Sidii la filayay, 9 bukaan ah (23%) waxay la kulmeen dhacdooyin xunxun. Ma jiro bukaan u joojiyay daaweynta sababo la xiriira dhacdooyinka xun ee difaaca. Marka la barbardhigo 11% ilaa 30% bukaanada ku jira tijaabada kiimikada labaad, natiijooyinka waxay ahaayeen kuwo aad loola yaabo. Marka la eego xaqiiqda ah in natiijooyinka badbaadada ee dhowaan tijaabooyinka bukaan-socodka ee kansarka caloosha ay saameeyeen khilaafaadka gobolka, Kei Muro iyo asxaabtiisuba waxay sii caddeeyeen in badbaadada bukaannada Aasiya iyo kuwa aan Aasiyaanka ahayn ee tijaabada Keynote-012 ay lamid tahay
Muujinta PD-L1 ma saadaalin kartaa waxtarka tallaalka difaaca jirka?
Tijaabada Keynote-012 waxay isticmaashaa immunohistochemistry si loo ogaado muujinta PD-L1. Bukaannada qaba unugyada burooyinka, unugyada difaaca ama labadan tiro unug waxay u baahan yihiin inay muujiyaan ugu yaraan 1% ee PD-L1 si ay ugu qalmaan tijaabada. Qoraaga ayaa markaa dib u qiimeeyay xaalada PD-L1 isagoo adeegsanaya tijaabooyin kala duwan. Natiijooyinka tijaabada labaad waxay muujinayaan in muujinta PD-L1 ee unugyada difaaca jirka, oo aan ahayn unugyada burooyinka, ay la xiriirto waxtarka pembrolizumab ee kansarka caloosha. Marka labaad, 8 ka mid ah 35 tijaabooyinka ka soo qaadista biopsy ee la qiimeyn karo waxay lahaayeen natiijo aan fiicnayn oo ah PD-L1. Natiijooyinkani waxay muujinayaan kakanaanta falanqaynta PD-L1 guud ahaan, gaar ahaan qiimeynta biomarkers ee kansarka caloosha. Leexashadani waxay u sabab noqon kartaa isbeddellada firfircoon ee muujinta PD-L1 daaweynta ka dib, kala duwanaanshaha hababka qiimeynta, iyo kaladuwanaanta kansarka caloosha. Sidaa darteed, ma cadda in tijaabooyinkii caafimaad ee la soo dhaafay ee aan lahayn baaritaanka biomarker, bukaanjiifka qaarkood ee u muuqda PD-L1 bukaanno taban oo qaatay daaweynta anti-PD1 ee cudur-ka-cafinta ay la xiriiraan kala duwanaanshaha muujinta biomarker, Ama haddii ay jirto xiriir dhab ah inta udhaxeysa biomarkers iyo waxtarka. Daraasad dheeraad ah ayaa loo baahan yahay
Habka ugu fiican ee lagu qiimeeyo muujinta PD-L1 iyo inay tahay run iyo waxtar saadaalin ku saleysan biomarker-ka kansarka caloosha ee difaaca jirka. Qorayaashu waxay sidoo kale soo wargeliyaan natiijooyinka hordhaca ah ee muujinta hiddo-wadaha gambar-ka ee loo yaqaan 'biomarker' ee saadaalinta unugyada aasaasiga ah ee saadaalinta madax-bannaan. Haddii natiijadan la xaqiijiyo, waxay kaa caawin kartaa in laga fogaado qaar ka mid ah dhibaatooyinka la xiriira immunohistochemistry mustaqbalka.
Arrimaha u baahan feker dheeri ah
Dabcan, tijaabo yar oo muunad ah sida Muhiimka ah-012 lama huraan waxay leedahay dhibaatooyinka qaar. Marka hore, ma cadda in uu jiro isdhexgal u dhexeeya daaweynta kiimikada ee la helay waagii hore iyo waxtarka pembrolizumab. In kasta oo bukaanjiifka wax u qabta ay heleen kaliya safka koowaad ama ka yar kiimiko ku daaweynta ka hor pembrolizumab, inta badan (63%) bukaanka ka jawaabaya waxay heleen layn labaad ama in ka badan oo lagula dagaallamo burooyinka. Intaa waxaa sii dheer, Keynote-012 waa muunad yar oo tijaabooyin caafimaad ah oo bilow ah laguma dari karo bukaanada badankood ee qaba kansarka gaaska ee horumarsan oo leh badbaado gaaban, taas oo laga yaabo inay ka dhigto heerarka jawaab celinta gaabiska ah iyo been-abuurka mararka qaarkood.
Natiijooyinka horumarka si dhib yar looma qancin karo. Dhowr tijaabo caafimaad oo socda ayaa isku dayaya inay go'aamiyaan daaqada ugufiican ee daaweynta daweynta bukaanka kansarka caloosha. Ta labaad, in kastoo aragti ahaan, bukaanka qaba kansarka caloosha ee leh microsomes aan degganeyn waa inay ku habboon yihiin tallaalka, iyo
Tijaabada Keynote-012, kala badh bukaanada qaba xasillooni darrada microsatelite-ka ee lagu daaweeyay pembrolizumab ayaa ka jawaabey. Qeybtan hoose ee kansarka caloosha waxay ka dhigan tahay 22% wadarta guud ee bukaanka kansarka caloosha waxayna mudan tahay daraasad dheeri ah. Ugu dambeyntiina, xuduudaha qiimeynaya natiijooyinka wanaagsan ee tijaabadan caafimaad ee daaweynta kansarka caloosha sidoo kale waxay u baahan tahay in si taxaddar leh loo tixgeliyo. Qiyaasta bukaanada la kulmay cudur daarista tijaabada Keynote-012 way kayartahay tii tijaabada RAINBOW ee paclitaxel iyo ramolizumab oo la isku daray. Xaqiiqdii, imtixaanka Keynote-012 waa mid aan fiicnayn oo laga soo qaatay qeexitaanka tirakoobka. Bukaanjiifka ka jawaabey daaweynta ma aysan muujin horumarin weyn oo ku saabsan badbaadada aan horumarka lahayn iyo guud ahaan badbaadada. Mustaqbalka, tijaabooyinka caafimaad ee socda waxay sidoo kale u baahan yihiin inay fiiro gaar ah u yeeshaan arrimahan.
Tijaabooyinka caafimaad ee la xiriira anti-CTLA-4 iyo daaweynta anti-PD-1 ayaa aad loogu guuleystay melanoma. Marka la barbardhigo, natiijooyinka tijaabada Keynote-012 waxay umuuqdaan kuwo xoogaa rajo qaba. Si kastaba ha noqotee, heerka dhimashada sannadlaha ah ee kansarka caloosha ee adduunka oo dhan waa saddex jeer ka badan kan melanoma ee xun, sidaas darteed natiijooyinka daraasaddan wali aad ayey muhiim u yihiin. Inta badan bukaannada kansarka caloosha ee aan haysan daaweyn wax ku ool ah, natiijooyinka hadda jira ayaa ah tallaabada ugu horreysa ee xiisaha leh ee lagu gaarayo muddada dheer ee ka-dhaafista cudurka Sannadihii ugu dambeeyay, caan ka ahaanshaha daaweynta jirka ee daaweynta kansarka ayaa sii kordheysa. Natiijooyinka hordhaca ah ee daraasadda Keynote-012 ee lagu qiimeynayo waxtarka PD-L1 inhibitor pembrolizumab ee bukaanada qaba kansarka gaaska ee horumarsan bishii Maajo 3, taas oo soo jiidatay fiiro badan.Professor Elizabeth C Smyth oo ka tirsan Isbitaalka Royal Marsden ee England ayaa tarjumay daraasadda, taas oo noo keeni karta xoogaa fikir iyo dhiirigalin ah.
Saadaalinta kansarka caloosha ee horumarsan waa mid liita, in ka yar 10-15% bukaanada metastatic ayaa noolaan kara in ka badan 2 sano. Trastuzumab iyo ramoluzumab oo loogu talagalay daaweynta safka labaad ee bukaanada kansarka caloosha ku dhaca ee HER2-positive waxay waxyar hagaajin karaan badbaadada guud. Sababtoo ah waxaa jira tusaalooyin badan oo ku saabsan fashilka dawooyinka daweynta ee ku saabsan qaybta kansarka caloosha, waxay umuuqataa in daawooyinkan ay gaareen guul yar. Xaaladdan adag ee hadda jirta ee daaweynta kansarka caloosha ee horumarsan, Daraasadda Muhiimka ah-012 ee ay sameeyeen Professor Kei Muro iyo asxaabtiisuba waxay markii hore muujiyeen natiijooyin wanaagsan, oo tilmaamaysa in ka hortagayaasha PD-L1 ay leeyihiin qiime daaweyn kara kansarka caloosha ee horumarsan.
Natiijooyinka ka soo baxay Daraasadda aaladda-012 waa wax lala yaabo
Daraasadda Keynote-012, bukaanada PD-L1-togan ee qaba kansarka gaaska ee horumarsan waxay heleen anti-PD-1 antibody pembrolizumab ilaa cudurka uu ka sii socdo ama dhacdooyin aan loo dulqaadan karin. Daraasadu waxay baartey wadarta bukaanada 162 ee qaba kansarka caloosha ee horumarsan, kuwaas oo 65 (40%) ay ku fiicnaadeen muujinta PD-L1, ugu dambeyntiina 39 (24%) bukaanno ayaa lagu qoray daraasaddan caalamiga ah ee Wajiga 1B. Si xiiso leh, 17 ka mid ah 32ka bukaan (53%) waxay la kulmeen dib-u-dhac buro; 8 ka mid ah 36 (22%) bukaanada leh waxtarka laqiimeyn karo waxay xaqiijiyeen in qeyb ahaan laga soo saaray. Qiyaasta cafiskaan waxay la jaanqaadaysaa natiijooyinka tijaabooyinka difaaca jirka ee kansarrada kale, oo leh jawaab celcelis dhexdhexaad ah oo 40 toddobaad ah, iyo 4 ka mid ah 36 bukaan (11%) leh cudur ka dhaafid ah ma muujin horumarka cudurka illaa waqtiga warbixinta. Sidii la filayay, 9 bukaan ah (23%) waxay la kulmeen dhacdooyin xunxun. Ma jiro bukaan u joojiyay daaweynta sababo la xiriira dhacdooyinka xun ee difaaca. Marka la barbardhigo 11% ilaa 30% bukaanada ku jira tijaabada kiimikada labaad, natiijooyinka waxay ahaayeen kuwo aad loola yaabo. Marka la eego xaqiiqda ah in natiijooyinka badbaadada ee dhowaan tijaabooyinka bukaan-socodka ee kansarka caloosha ay saameeyeen khilaafaadka gobolka, Kei Muro iyo asxaabtiisuba waxay sii caddeeyeen in badbaadada bukaannada Aasiya iyo kuwa aan Aasiyaanka ahayn ee tijaabada Keynote-012 ay lamid tahay
Muujinta PD-L1 ma saadaalin kartaa waxtarka tallaalka difaaca jirka?
Tijaabada Keynote-012 waxay isticmaashaa immunohistochemistry si loo ogaado muujinta PD-L1. Bukaannada qaba unugyada burooyinka, unugyada difaaca ama labadan tiro unug waxay u baahan yihiin inay muujiyaan ugu yaraan 1% ee PD-L1 si ay ugu qalmaan tijaabada. Qoraaga ayaa markaa dib u qiimeeyay xaalada PD-L1 isagoo adeegsanaya tijaabooyin kala duwan. Natiijooyinka tijaabada labaad waxay muujinayaan in muujinta PD-L1 ee unugyada difaaca jirka, oo aan ahayn unugyada burooyinka, ay la xiriirto waxtarka pembrolizumab ee kansarka caloosha. Marka labaad, 8 ka mid ah 35 tijaabooyinka ka soo qaadista biopsy ee la qiimeyn karo waxay lahaayeen natiijo aan fiicnayn oo ah PD-L1. Natiijooyinkani waxay muujinayaan kakanaanta falanqaynta PD-L1 guud ahaan, gaar ahaan qiimeynta biomarkers ee kansarka caloosha. Leexashadani waxay u sabab noqon kartaa isbeddellada firfircoon ee muujinta PD-L1 daaweynta ka dib, kala duwanaanshaha hababka qiimeynta, iyo kaladuwanaanta kansarka caloosha. Sidaa darteed, ma cadda in tijaabooyinkii caafimaad ee la soo dhaafay ee aan lahayn baaritaanka biomarker, bukaanjiifka qaarkood ee u muuqda PD-L1 bukaanno taban oo qaatay daaweynta anti-PD1 ee cudur-ka-cafinta ay la xiriiraan kala duwanaanshaha muujinta biomarker, Ama haddii ay jirto xiriir dhab ah inta udhaxeysa biomarkers iyo waxtarka. Daraasad dheeraad ah ayaa loo baahan yahay
Habka ugu fiican ee lagu qiimeeyo muujinta PD-L1 iyo inay tahay run iyo waxtar saadaalin ku saleysan biomarker-ka kansarka caloosha ee difaaca jirka. Qorayaashu waxay sidoo kale soo wargeliyaan natiijooyinka hordhaca ah ee muujinta hiddo-wadaha gambar-ka ee loo yaqaan 'biomarker' ee saadaalinta unugyada aasaasiga ah ee saadaalinta madax-bannaan. Haddii natiijadan la xaqiijiyo, waxay kaa caawin kartaa in laga fogaado qaar ka mid ah dhibaatooyinka la xiriira immunohistochemistry mustaqbalka.
Arrimaha u baahan feker dheeri ah
Dabcan, tijaabo yar oo muunad ah sida Muhiimka ah-012 lama huraan waxay leedahay dhibaatooyinka qaar. Marka hore, ma cadda in uu jiro isdhexgal u dhexeeya daaweynta kiimikada ee la helay waagii hore iyo waxtarka pembrolizumab. In kasta oo bukaanjiifka wax u qabta ay heleen kaliya safka koowaad ama ka yar kiimiko ku daaweynta ka hor pembrolizumab, inta badan (63%) bukaanka ka jawaabaya waxay heleen layn labaad ama in ka badan oo lagula dagaallamo burooyinka. Intaa waxaa sii dheer, Keynote-012 waa muunad yar oo tijaabooyin caafimaad ah oo bilow ah laguma dari karo bukaanada badankood ee qaba kansarka gaaska ee horumarsan oo leh badbaado gaaban, taas oo laga yaabo inay ka dhigto heerarka jawaab celinta gaabiska ah iyo been-abuurka mararka qaarkood.
Natiijooyinka horumarka si dhib yar looma qancin karo. Dhowr tijaabo caafimaad oo socda ayaa isku dayaya inay go'aamiyaan daaqada ugufiican ee daaweynta daweynta bukaanka kansarka caloosha. Ta labaad, in kastoo aragti ahaan, bukaanka qaba kansarka caloosha ee leh microsomes aan degganeyn waa inay ku habboon yihiin tallaalka, iyo
Tijaabada Keynote-012, kala badh bukaanada qaba xasillooni darrada microsatelite-ka ee lagu daaweeyay pembrolizumab ayaa ka jawaabey. Qeybtan hoose ee kansarka caloosha waxay ka dhigan tahay 22% wadarta guud ee bukaanka kansarka caloosha waxayna mudan tahay daraasad dheeri ah. Ugu dambeyntiina, xuduudaha qiimeynaya natiijooyinka wanaagsan ee tijaabadan caafimaad ee daaweynta kansarka caloosha sidoo kale waxay u baahan tahay in si taxaddar leh loo tixgeliyo. Qiyaasta bukaanada la kulmay cudur daarista tijaabada Keynote-012 way kayartahay tii tijaabada RAINBOW ee paclitaxel iyo ramolizumab oo la isku daray. Xaqiiqdii, imtixaanka Keynote-012 waa mid aan fiicnayn oo laga soo qaatay qeexitaanka tirakoobka. Bukaanjiifka ka jawaabey daaweynta ma aysan muujin horumarin weyn oo ku saabsan badbaadada aan horumarka lahayn iyo guud ahaan badbaadada. Mustaqbalka, tijaabooyinka caafimaad ee socda waxay sidoo kale u baahan yihiin inay fiiro gaar ah u yeeshaan arrimahan.
Tijaabooyinka caafimaad ee la xiriira anti-CTLA-4 iyo daaweynta anti-PD-1 ayaa aad loogu guuleystay melanoma. Marka la barbardhigo, natiijooyinka tijaabada Keynote-012 waxay umuuqdaan kuwa waxyar rajo qaba. Si kastaba ha noqotee, heerka dhimashada sanadlaha ah ee kansarka caloosha ee adduunka oo dhan waa saddex jeer ka badan kan melanoma ee xun, sidaas darteed natiijooyinka daraasaddan wali aad ayey muhiim u yihiin. Inta badan bukaannada kansarka caloosha ee aan haysan daaweyn wax ku ool ah, natiijooyinka hadda jira ayaa ah tallaabada ugu horreysa ee xiisaha leh ee lagu gaarayo cudur-ka-qaadista muddada-dheer.
