Immunotherapy daaweynta kansarka sanbabka, kansarka sanbabada immunotherapy, kansarka sanbabada PD-1 daawaynta, iyo kansarka sanbabada PD-L1 oo dhan waxaad rabto in aad ogaato.
In the past two years, immune checkpoint inhibitors have undoubtedly been one of the most successful tumor immunotherapies, which has changed the treatment prospects for NSCLC. The four PD-1 / L1 currently approved for lung cancer have improved the five-year survival rate of advanced lung cancer from less than 5% to 16%, which has tripled, and many patients and even doctors are excited. Immunotherapy is gradually becoming a “special effect” drug for the treatment of advanced kansarka sanbabada ee aan yareyn. Most kansarka sanbabada patients still have many questions about PD-1 treatment, and today we will answer them one by one.
Waa maxay daaweynta PD-1 / L1 ee kansarka sanbabada?
Immunotherapy is a therapy that uses the patient’s immune system to fight cancer. PD-1 / L1 treatment is called immune checkpoint inhibitor therapy and is a type of immunotherapy.
Daaweynta isbaarada isbaarada ee difaaca waxaa loola jeedaa: PD-1 waa borotiin ku yaal dusha sare ee unugyada T kaas oo gacan ka geysta xakameynta jawaabta difaaca jirka. Marka PD-1 ay ku xidho borotiin kale oo loo yaqaan PDL-1 oo ku saabsan unugyada kansarka, waxay ka hortagtaa unugyada T (unuga difaaca) inay dilaan unugyada kansarka. PD-1 inhibitor-ku wuxuu ku xidhan yahay PDL-1, si uu u sii daayo xakamaynta difaaca ee unugyada T oo uu dib u helo awoodda uu ku dilo unugyada kansarka.
Maxay yihiin PD-1 / L1 ee hadda ay ansixisay FDA daaweynta kansarka sanbabada?
FDA waxay ansixisay afar isbaaro isbaaro oo difaac ah: Nivolumab (O drug), pembrolizumab (Daawoyinka K), atezolizumab (daroogada T) iyo durvalumab (I dawada) ee daawaynta kansarka sambabada unugyada aan yarayn.
| Magaca Daroogada | Pembrolizumab | Nivolumab | Attuzumab | Devaruzumab |
| Magaca Ingiriisiga | keytruda | Cajiib | Tecentriq | Imfifinzi |
| saaraha | Merck | Bristol-Myers | Roche | AstraZeneca |
| qiyaasta | 2mg / kg saddexdii toddobaadba mar | 3mg / kg labadii usbuucba mar | 1200mg saddexdii toddobaadba mar | 10mg / kg labadii usbuucba mar |
| Qorista | Liiska Mareykanka | Liis gareysan Shiinaha | Liiska Mareykanka | Ku qoran Shiinaha |
Maxay yihiin tilmaamaha lagu ogaanayo kansarka sanbabada PD-1 / L1 ogolaansho kasta?
Pabolizumab (Pembrolizumab, Pambrolizumab, Pembrolizumab) | Kerui Da (Jinheide, Keytruda) | K daroogada
| Tilmaamaha la oggol yahay (kansarka sanbabada) | In la ogaado PD-L1 |
| 1. Ku darmay pemetrexed iyo cisplatin / karboplatin daaweynta ugu horeysa ee daaweynta aan la kala soocikarin, dib u noqoshada / dib u noqoshada non-squamous non-small cell cancer cancer (NSCLC), iyadoon loo eegin muujinta PD-L1 | maya |
| 2. Lagu daro karboplatin iyo paclitaxel / nab-paclitaxel (Abraxane) oo loogu talagalay bukaanka qaba kansarka sanbabada ee unugyada yar-yar ee soo noqnoqda / soo noqnoqda ee aan lagu gaari karin daaweynta safka hore, iyadoo aan loo eegin muujinta PD-L1 | maya |
| 3. Single-agent, first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC), whose metastatic non-small cell lung cancer (NSCLC) tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%], by FDA approved test confirms that there are no EGFR or ALK genome buro aberrations | Haa, PD-L1≥50% |
| 4. Daawaynta kelida ah ee bukaanka qaba kansarka sambabada unugyada unugyada yaryar ee metastatic (NSCLC), kuwaas oo buradu ay muujinayso PD-L1 ((TPS) ≥ 1%), oo ay go'aamisay tijaabooyinka FDA la ansixiyay, horumarka cudurka ka dib daaweynta kemotherabi ku salaysan platinum | Haa, PD-L1 ≥ 1% |
Nivolumab (Navumab, Niluumab, Nivolumab) | Odivo (Odivo, Odvo, Opdivo) | O daroogada
| Tilmaamaha la oggol yahay (kansarka sanbabada) |
| 1. Daaweynta kansarka sanbabada ee unugyada aan-yareyn (heer sare) ee wali kujira daaweynta kiimikada ee platinum |
| 2. Daaweynta bukaanada qaba kansarka sanbabada ee unugyada yar-yar (metastatic) squamous non-small cell cell (NSCLC), oo ku haboon bukaanada leh daaweynta kiimikada ku saleysan platinum ama cudurka uu ka sii daray ka dib daaweynta kemotherabi |
Devarizumab (Duvaluzumab, Duvalizumab, Deluzumab, Durvalumab) | Waxaan daroogo (Imfinzi)
| Tilmaamaha la oggol yahay (kansarka sanbabada) |
| Waxaa loo isticmaalaa in lagu daaweeyo kansarka sanbabada ee unugyada yar-yar (NSCLC) ee aan soo marin qalliin qalliin kadib markii uu maray heerarka caadiga ah ee platinum-ku-saleysan radiochemotherapy |
Attuzumab (Atezolizumab, Atezolizumab) | T daroogada (Tecentriq)
| Tilmaamaha la oggol yahay (kansarka sanbabada) |
| 1. Kansarka sambabka unugyada unugyada unugyada 'metastatic non-yar' oo kansarka sanbabada oo xaaladoodu ka sii darto inta lagu jiro ama ka dib daweynta kiimoteraatiga ee ku jira platinaum. Haddii kansarka sanbabada ee unugyada yar ee bukaanku isbadalo EGFR ama hiddo-wadaha ALK, daawooyinka bartilmaameedka kelli ah ee bartilmaameedsanaya EGFR ama hiddo-wadaha ALK waa in marka hore la adeegsadaa, iwm. |
| 2. Isku dar ah kemotherabi (Abraxane [paclitaxel protein conjugate; nab-paclitaxel] iyo karboplatin) oo ah daaweynta ugu horeysa ee bukaanada qaba kansarka sanbabada unugyada unugyada unugyada yar-yar ee non-squamous non-small cell (NSCLC) oo aan lahayn EGFR ama ALK |
Sida loo doorto PD-1 / L1 bukaanka qaba kansarka sanbabada
Sida loo doorto afarta kahortagayaasha isbaarooyinka difaaca jirka waa mid ka mid ah dhibaatooyinka ugu welwelka badan ee bukaanka kansarka sanbabada. Jadwalka soo socda ayaa si kooban oo cad u soo koobaya xulashada qorshaha daaweynta ee qof walba.
Kansarka sambabka unugyada unugyada aan-yareyn
Daaweynta-koowaad ee tallaalka kansarka sanbabada ee horumarsan
| Layered | Talada heerka koowaad | Talada Heerka 3aad |
| PD-L1≥50% | Daaweynta Pembrolizumab | |
| 1% ≤PD-L1≤49% | Kansarka unugyada 'squamous cell carcinoma': Pabolizumab
Kansarka unugyada non-squamous carcinoma: Pabolizumab hal daroogo ama Pabolizumab oo lagu daro platinum + pemetrexed |
|
| PD-L1 ＜ 1% ama aan la garanayn | Kansarka unugyada aan-xajmiga lahayn: paclizumab oo lagu daro platinum + pemetrexed | Non-squamous cell carcinoma: atezumab combined with bevacizumab combined with chemotherapy (carboplatin and paclitaxel) |
Tallaalka-labaad ee tallaalka kansarka sanbabada ee horumarsan
| Layered | Talada heerka koowaad | Talada Heerka 3aad |
| Ma jirin daaweyn hore PD-1 / L1 | PD-L1 lama yaqaan ama iyadoon loo eegin heerka muujinta: nivolumab monotherapy | PD-L1 lama yaqaan ama aan loo eegin xaaladda muujinta: atezumab monotherapy |
| Daaweyntii hore ee PD-1 / L1 | Daaweyntii hore ee PD-1 / L1: daaweynta platinum waa in lagu daraa daaweynta kiimoteraabiga ah (dooro kemotherabi habboon sida ku xusan nooca taariikhiga ah)
Daaweynta hore ee PD-1 / L1 ee lagu daweynayo kiimoterapi: docetaxel ama kiimiko kale oo hal-wakiil ah (daroogada koowaad ee aan la helin) |
Tallaalka saddexaad ee tallaalka loogu talagalay kansarka sanbabada ee horumarsan: talobixin labaad, nivolumab.
Kansarka sambabada unugyada aan yarayn ee saddex-heer ah oo aan la silcin karin: Talada fasalka III, helitaanka daawaynta xoojinta dufaliolizumab ka dib daaweynta shucaaca iyo kiimoterabiga.
Cel-aan-yareyn
l kansarka sanbabada oo leh isbeddel
Daaweynta tallaalka ee NSCLC oo leh EFGR / ALK togan, weli waxaa jira caddayn ku filan. Natiijooyinka falanqaynta koox-kooxeedka IMpower150 waxay muujinayaan in qorshaha soo socda uu leeyahay saameyn gaar ah: atelizumab + bevacizumab + karboplatin + taxol
Tilmaamahee ayaa u baahan in la tijaabiyo ka hor inta aan la isticmaalin PD-1 / L1?
Waqtigan xaadirka ah, daaweeyayaashu waxay tixraacayaan muujinta TMB iyo PD-L1 inay yihiin astaamo loogu talagalay daaweynta sanbabada iyo daaweynta kiimikada. Rossy wuxuu kuu diyaariyay maqaal aad ku turjumeyso shanta biomarkers ee saadaalinaya waxtarka PD-1. Waxaad u gudbin kartaa: Sidee loo sii saadaaliyaa waxtarka PD-1 ka hor? Falanqeyn ballaaran oo ku saabsan shanta saadaaliye ee waaweyn!
1) PD-L1
Waqtigan xaadirka ah, waxaa loo tixgeliyaa in muujinta PD-L1 ee unugyada burooyinka ay tahay calaamadee macquul ah oo lagu xusho tirada dadka ka hor daaweynta anti-PD-1 / PD-L1. Laakiin isla mar ahaantaana, dhibaatooyin badan ayaa ka jira ogaanshaha PD-L1, sida kaladuwanaanta hawada, qayb yar oo ka mid ah burooyinka ma meteli kartaa gobolka oo dhan buro dhan? Sidoo kale waxaa jira kala duwanaansho kumeelgaar ah, maxaa yeelay daaweynta ka dib, PD-L1's Xaaladda muujinta ayaa is beddeli doonta. Ma jiraan wax jaan-goyn ah oo lagu ogaanayo habka difaaca jirka. Waxaa jira unugyo badan oo difaaca jirka ah oo loogu talagalay wasakheynta difaaca jirka ee PD-L1. Qiyaasta heshiiska wanaagsan ee unugyada difaaca jirka waa 73% -76% oo keliya, taas oo saameyn ku yeelan doonta natiijooyinka ogaanshaha.
2) TMB
Cilmi-baarista hadda jirta waxay muujineysaa in TMB / bTMB ay tahay calaamadeeye saadaalin ah oo ku saabsan saameynta daaweynta ee ICIs weli waa muran.
Bukaannada guryaha ku jira ee hadda laga helay kansarka sanbabada ee unugyada aan yareyn, warshadaha daaweynta kansarka sanbabada guud ahaan waxay kugula talinayaan baaritaanka PD-L1. Haddii PD-L1 ≥ 50%, ha ahaato kansarka unugyada unugyada unugyada unugyada 'carcanooma cell cell carcinoma' ama 'non squamous cell carcinoma', cusub ee la daweeyay, hiddo-wadaha aan hiddo-wadaha ahayn ee bukaanka kansarka unugyada unugyada yaryar ayaa lagu daaweyn karaa daawooyinka K si loo helo fursadda ugu weyn ee badbaadada badbaadada waqtigan xaadirka ah.
Dabcan, marka loo eego adeegsiga caafimaad ee kahortagayaasha isbaarooyinka difaaca, Mareykanka ayaa ah midka ugu cilmi baarista badan wuxuuna leeyahay khibradda caafimaad ee ugu qanisan. Khubarada awooda u leh cudurka kansarka sanbabada ee Mareykanka waxay ku saleysan yihiin macluumaadka hada jira ee TMB iyo PD-L1 ee daaweynta kiimikada iyo / ama difaaca jirka ee kansarka sanbabada Bukaanjiifka waa la xannibay.
1. Daaweynta monotherapy ee anti-PD-1 waxaa la siiyaa bukaanada qaba burooyinka "kulul" ama burooyinka bararsan leh muujinta sare ee PD-L1 iyo TMB.
2. Bukaannada qaba muujinta PD-L1 ee sare laakiin TMB hooseeya, sii daaweenta kiimikada.
3. Bukaannada qaba TMB sare laakiin muujinta PD-L1 hooseeya ama taban, sii daaweyn kiimiko ama daaweynta anti-PD-1 / CTLA-4.
4. Intaa waxaa dheer, bukaanada qaba "qabow" ama burooyin aan xanuun lahayn oo leh TMB hooseeya iyo muujinta hoose ama taban ee PD-L1, daaweynta kiimikada waxaa lagu sameeyaa iyada oo aan lahayn ama aan lahayn immunotherapy ama unugyada difaaca jirka ee suurtogalka ah.
Rossy wuxuu xasuusinayaa bukaanada kansarka sanbabada badankood kahor intaan la isticmaalin PD-1, waa inay doortaan shirkad awood uleh baaritaanka biomarker, kadibna la tasho Bei Shangguang ama xitaa khabiir caan ku ah kansarka sanbabada ee Mareykanka si loo sameeyo qorshe daawo oo sax ah. , ama waxay la tashan karaan dhakhtarka kansarka adduunka. Waaxda Daaweynta Webka.
Bukaanada PD-1 ee leh aragti hooseeya ma isticmaali karaan PD-1?
Bukaannada qaba unugyada kansarka unugyada aan yaryar ahayn ee hadda la ogaaday, illaa iyo inta muujinta PD-L1 ay tahay mid wanaagsan, ha ahaato kansarka unugyada unugyada 'carnoma' ama 'non-squamous cell carcinoma', waxaa suurtagal ah in laga helo faa'iidooyinka badbaadada bilowga hore daaweynta monoterapi K-daweynta, taas oo kordhinaysa nolosha. Khubarada qaar ayaa sidoo kale soo jeedinaya in bukaanada qaba muujinta PD-L1 inta u dhaxeysa 1-49% ay sidoo kale isticmaali karaan K oo lagu daweynayo kemotherabi haddii ay u dulqaadan karaan kemotherabi.
Ma loo isticmaali karaa PD-1 bukaanada dhowaan la daweeyey ee leh baaritaanka PD-L1 ee taban?
Natiijooyinka ugu dambeeya ee badan ee PD-1 monoclonal antibody isku dhafan daraasadaha kiimoteraabiga ayaa cadeeyay in xitaa haddii baaritaanka PD-L1 uu yahay mid xun, ama PD-L1 aan lagu tijaabin xaalad ahaan, PD-1 monoclonal antibody oo lagu daro kemotherabi ayaa daaweyn kara unugyada kansarka unugyada ama kuwa aan squamous ahayn kansarka unugyada. Bukaannada kansarka sanbabada gacanta waxay keeneysaa faa'iidooyin badbaado oo aad u muhiim ah oo leh daaweynta kiimikada oo keliya.
Bukaannada qaba PD-L1-kansarka sambabka unugyada unugyada aan-yareyn, iyadoon loo eegin inay leeyihiin kansarka sanbabada unugyada unugyada yar yar ama kuwa aan squamous ahayn, haddii aysan horay u helin daaweynta kiimoteraad, ka dib markay heleen K isku daweynta kiimoterapi, marka la barbardhigo kemotherabi oo keliya Bukaanada oo dhami waxay heli karaan dheefo badbaado oo dheer. Xogta noocan oo kale ah waa war wanaagsan oo loogu talagalay bukaanada qaba muujinta PD-L1 ee xun ama aan lahayn xaalad lagu ogaanayo PD-L1.
Bukaannada ku jira kiimoteraabiga ma u wareegi karaan ama ku dari karaan PD-1?
Iyadoo aan loo eegin hadday tahay kansarka unugyada unugyada unugyada unugyada 'squamous' ama 'non squamous non-small cell cancer', saameynta K ee lagu daweynayo kemotherabi xaqiiqdii way ka fiicantahay daaweynta kemotherabi oo keliya, laakiin bukaanada qaata kiimoteraabiga ma heli karaan PD-1 monoclonal antibody? Waa maxay saameynta ugu wanaagsan ee kiimoteraabiga?
Ka dib shucaaca iyo kemotherabi ka dib, waxay dili doontaa unugyada burooyinka qaarkood, taas oo sii deyn doonta antigens-ka burooyinka iyo kicinta difaacyada aadanaha. Waqtigaan, haddii daaweynta PD-1 monoclonal antibody la siiyo, aragti ahaan, saameynta kahortaga burooyinka way sii xoogeysan doontaa. Waqtigan xaadirka ah, waxaa jira natiijooyin cilmi baaris hordhac ah oo muujinaya in daaweynta dayactirka difaaca ee PD-1 monoclonal antibody ama PD-L1 monoclonal antibody ka dib shucaaca isku midka ah iyo daaweynta kiimikada ay leedahay saameyn wanaagsan oo si weyn u dheereysa nolosha.
Bukaannada hadda la ogaaday waa inay marka hore bilaabaan daaweynta kemotherabi, ka dibna doortaan PD-1 ama ay u isticmaalaan PD-1 si toos ah daawada iska caabinta ka dib.
Bukaannada qaba kansarka unugyada aan yarayn ee horumarsan ee hadda la ogaaday, isticmaalka hore ee PD-1 monoclonal antibody waxay u keeneysaa faa'iidooyin badbaado oo ka wanaagsan isticmaalka dambe.
Maxaa la sameeyaa ka dib iska caabinta PD-1?
Bukaannada qaba wax-qabadka wax-ku-oolka ah ee PD-1 guud ahaan waxay leeyihiin saameyn muddo dheer socota; si kastaba ha noqotee, qiyaastii 30% bukaannada ayaa loo arkay inay leeyihiin iska caabin cudur. Furaha looga guuleysto iska caabinta daroogada ayaa badiyaa ah laba qodob:
Marka hore, haddii ay suurtagal tahay, biopsy iyo falanqaynta qotada dheer ee difaaca jirka waxaa lagu sameyn karaa goobaha cusub ee lagu darey ama sii kordhaya ee iska caabinta daroogada si loo helo sababta keenta iska caabinta daroogada loona daaweeyo iyadoo loo eegayo sababta. Tusaale ahaan, bukaanjiifka qaar waxaa sabab u ah muujinta sare ee magdhowga ee TIM-3, LAG-3 ama IDO; ka dib dooro, PD-1 inhibitor oo lagu daro TIM-3 inhibitor, LAG-3 antibody, IDO inhibitor waa xalka daaweynta ugu fiican.
Marka labaad, bukaanka aan go'aamin karin sababta keentay iska caabinta daroogada, waxay isku dari karaan shuruudaha gaarka ah si ay u doortaan lamaanaha wadajirka ah ee ugu fiican ee ka noqda iska caabbinta daroogada iyo sii dheereynta noolaanshaha; ama, u wareeji daaweynta caadiga ah sida shucaaca iyo daaweynta kiimikada, faragelinta, soo noqnoqodka raadiyaha, iyo abuurista unugyada.
Ugu dambeyntiina, iyo tan ugu muhiimsan, caddayn iyo inbadan oo ka mid ah waxay taageertaa in difaaca jirka sida PD-1 inhibitors loo isticmaalo sida ugu dhakhsaha badan ee suurtogalka ah marka xaaladda guud ee bukaanku ka fiicnaato oo culeyska burooyinka uu yaraa
