amakuru

Kanseri y'ibihaha itari ntoya (NSCLC) igera kuri 80% -85% by'umubare rusange wa kanseri y'ibihaha, kandi kubaga ni bwo buryo bwiza bwo kuvura bikabije NSCLC yo hambere. Ariko, hamwe no kugabanukaho 15% gusa kubisubiramo no gutera imbere 5% mubuzima bwimyaka 5 nyuma ya chimiotherapie ya perioperative, harakenewe ivuriro rinini ridakenewe.

Perioperative immunotherapy kuri NSCLC ni ubushakashatsi bushya mu myaka yashize, kandi ibisubizo by'ibice byinshi byo mu cyiciro cya 3 byateganijwe byateganijwe byagaragaje umwanya w'ingenzi wo gukingira indwara ya perioperative.

Immunotherapie ku barwayi bafite kanseri yo mu cyiciro cya mbere kitari gito kanseri y'ibihaha (NSCLC) yateye intambwe igaragara mu myaka yashize, kandi ubu buryo bwo kuvura ntibwongerera ubuzima bw'abarwayi gusa, ahubwo binazamura imibereho myiza, butanga inyongera ifatika ku kubaga gakondo

Ukurikije igihe immunotherapi itangiwe, hariho uburyo butatu bwingenzi bwo gukingira indwara mukuvura hakiri kare NSCLC:

1. Neoadjuvant immunotherapy yonyine: Immunotherapy ikorwa mbere yo kubagwa kugirango igabanye ubunini bwikibyimba kandi igabanye ibyago byo kongera kubaho. Ubushakashatsi bwa CheckMate 816 [1] bwerekanye ko immunotherapie hamwe na chimiotherapie byateje imbere cyane kubaho nta byabaye (EFS) mu cyiciro cya neoadjuvant ugereranije na chimiotherapie yonyine. Byongeye kandi, immunoterapi ya neoadjuvant irashobora kandi kugabanya igipimo cyisubiramo mugihe itezimbere igipimo cy’ibisubizo byuzuye by’abarwayi, bityo bikagabanya amahirwe yo kongera kwibaruka.
2. Imiti ikingira indwara (neoadjuvant + adjuvant): Muri ubu buryo, immunotherapie itangwa mbere na nyuma yo kubagwa kugirango igabanye ingaruka mbi za antitumor kandi ikureho ibikomere bike byasigaye nyuma yo kubagwa. Intego nyamukuru yubu buryo bwo kuvura ni ukuzamura ubuzima bwigihe kirekire no gukiza igipimo cy’abarwayi b’ibibyimba bahuza immunotherapie kuri neoadjuvant (pre-operative) na adjuvant (post-operasiyo). Keykeynote 671 ni uhagarariye iyi moderi [2]. Nkikigereranyo cyonyine cyateganijwe kugenzurwa (RCT) hamwe nibyiza bya EFS na OS, cyasuzumye imikorere ya palizumab ihujwe na chimiotherapie mubyiciro bidasubirwaho Ⅱ, ⅢA, na ⅢB (N2) abarwayi ba NSCLC. Ugereranije na chimiotherapie yonyine, pembrolizumab ifatanije na chimiotherapie yongereye hagati ya EFS imyaka 2,5 kandi bigabanya ibyago byo kwandura indwara, kongera kubaho, cyangwa gupfa 41%; KEYNOTE-671 nubundi bushakashatsi bwa mbere bw’ubudahangarwa bwerekanye inyungu rusange yo kubaho (OS) muri NSCLC ishobora kwangirika, aho byagabanutseho 28% ibyago byo gupfa (HR, 0,72), intambwe yibanze muri neoadjuvant hamwe n’ubudahangarwa bw’ubuvuzi bwa NSCLC.

3. Adjuvant immunotherapy yonyine: Muri ubu buryo, abarwayi ntibigeze bavurwa mbere yo kubagwa, kandi immunodrugs yakoreshejwe nyuma yo kubagwa kugira ngo hirindwe ko ibibyimba bisigaye, bikwiranye n’abarwayi bafite ibyago byinshi byo kongera kubaho. Ubushakashatsi bwa IMpower010 bwasuzumye imikorere ya attilizumab nyuma yubuvuzi hamwe nubuvuzi bwiza bufasha abarwayi bafite icyiciro cya IB kugeza IIIA (AJCC 7 Edition) NSCLC [3]. Ibisubizo byerekanye ko kuvura hamwe na attilizumab byongerewe igihe kirekire kubaho nta ndwara (DFS) mu barwayi ba PD-L1 ku cyiciro cya ⅱto ⅢA. Byongeye kandi, ubushakashatsi bwa KEYNOTE-091 / PEARLS bwasuzumye ingaruka za pembrolizumab nk'ubuvuzi bufatika ku barwayi batewe burundu bafite icyiciro cya IB kugeza IIIA NSCLC [4]. Pabolizumab yongerewe igihe kinini mubaturage muri rusange (HR, 0,76), hamwe na DFS yo hagati y'amezi 53,6 mumatsinda ya Pabolizumab n'amezi 42 mumatsinda ya placebo. Mu itsinda ry’abarwayi bafite amanota y’ibibyimba bya PD-L1 (TPS) ≥50%, nubwo DFS yongerewe igihe kinini mu itsinda rya Pabolizumab, itandukaniro riri hagati yaya matsinda yombi ntabwo ryagaragaye cyane mu mibare bitewe n’ubunini bw’icyitegererezo, kandi byari bikenewe gukurikiranwa kugira ngo byemeze.

Ukurikije niba immunotherapie ihujwe nindi miti cyangwa ingamba zo kuvura nuburyo bwo guhuza, gahunda yo gukingira indwara ya neoadjuvant hamwe nubudahangarwa bw'umubiri irashobora kugabanywamo uburyo butatu bukurikira:

1. Ubudahangarwa bumwe: Ubu bwoko bwo kuvura bukubiyemo ubushakashatsi nka LCMC3 [5], IMpower010 [3], KEYNOTE-091 / PEARLS [4], BR.31
2. Guhuza immunotherapie na chimiotherapie: Ubushakashatsi nkubu burimo KEYNOTE-671 [2], CheckMate 77T [8], AEGEAN [9], RATIONALE-315 [10], Neotorch [11], na IMpower030 [12]. Ubu bushakashatsi bwarebye ingaruka zo guhuza immunotherapie na chimiotherapie mugihe cya perioperative.
3. Guhuza immunotherapie nubundi buryo bwo kuvura: (1) Guhuza nizindi immunodrugs: Urugero, cytotoxic T lymphocyte ifitanye isano na antigen 4 (CTLA-4) yahujwe na test ya NEOSTAR [13], lymphocyte activation gene 3 (LAG-3) antibody yahujwe na test ya NIM-Predict-Lung [14], na T selile immunogl TIGIT antibody ikomatanya [15] yongereye imbaraga zo kurwanya ibibyimba hifashishijwe imiti ikingira indwara. . . Ubushakashatsi bwuburyo bwinshi bwo gukingira indwara bwerekana ko uburyo bwo gukoresha immunotherapie mugihe cya perioperative butarasobanuka neza. Nubwo ubudahangarwa bw'umubiri bwonyine bwerekanye umusaruro ushimishije mu kuvura perioperative, mu guhuza imiti ya chimiotherapie, imiti ivura imirasire, imiti igabanya ubukana, hamwe n’indi miti igabanya ubukana nka CTLA-4, LAG-3, na TIGIT, abashakashatsi bizeye kurushaho kuzamura imikorere y’ubudahangarwa bw'umubiri.

Haracyari umwanzuro ku buryo bwiza bwo gukingira indwara ya NSCLC ikoreshwa hakiri kare, cyane cyane niba immunotherapy ya perioperative ugereranije na neoadjuvant immunotherapy yonyine, kandi niba hari ubundi buryo bwo gukingira indwara bushobora kuzana izindi ngaruka zikomeye, haracyari ikibazo cy’ibigereranyo byagereranijwe.
Forde n'abandi. yakoresheje ubushakashatsi bwerekana amanota aremereye kugirango agereranye ingaruka z ibigeragezo byateganijwe, kandi ahindura imibare fatizo y’imibare n’ibiranga indwara mu baturage batandukanye biga kugira ngo agabanye ingaruka ziterwa n’ibi bintu, bituma ibisubizo bya CheckMate 816 [1] na CheckMate 77T [8] bigereranywa. Igihe cyo gukurikiranwa hagati cyari amezi 29.5 (CheckMate 816) n'amezi 33.3 (CheckMate 77T), gitanga umwanya uhagije wo gukurikirana EFS nizindi ngamba zingenzi zikorwa.
Mu isesengura riremereye, HR ya EFS yari 0,61 (95% CI, 0.39 kugeza 0.97), byerekana ko 39% ibyago byo kongera kubaho cyangwa gupfa muri perioperative nabuliumab ihuriweho na chimiotherapie (CheckMate 77T mode) ugereranije na neoadjuvant nabuliumab ihuriweho na chimiotherapie (CheckMate 816). Perioperative nebuliuzumab hiyongereyeho na chimiotherapie itsinda ryerekanye inyungu zoroheje kubarwayi bose bari murwego rwibanze, kandi ingaruka zagaragaye cyane kubarwayi bafite ibibyimba bitageze kuri 1% PD-L1 (kugabanya 49% ibyago byo kongera kubaho cyangwa gupfa). Byongeye kandi, kubarwayi bananiwe kugera kuri pCR, perioperative nabuliumab ihuriweho na chimiotherapie yerekanaga inyungu nyinshi za EFS (kugabanya 35% ibyago byo kongera kubaho cyangwa gupfa) kuruta neoadjuvant nabuliumab ihuriweho na chimiotherapie. Ibi bisubizo byerekana ko uburyo bwo gukingira indwara ya perioperative bugira akamaro kuruta uburyo bwa immunotherapy bwa neoadjuvant bwonyine, cyane cyane ku barwayi bafite imvugo ya PD-L1 nkeya hamwe n’ibisigisigi by’ibibyimba nyuma yo kuvurwa bwa mbere.
Nyamara, kugereranya bimwe mu buryo butaziguye (nka meta-gusesengura) byagaragaje ko nta tandukaniro rinini riri hagati yo kubaho hagati ya immunotherapy ya neoadjuvant na immunotherapy ya perioperative [18]. Isesengura ryakozwe rishingiye ku mibare y’abarwayi ku giti cyabo ryerekanye ko immunotherapy ya perioperative na immunootherapie ya neoadjuvant yagize ibisubizo bisa kuri EFS haba mu matsinda ya pCR ndetse n’abatari PCR ku barwayi bafite NSCLC yo mu cyiciro cya mbere [19]. Byongeye kandi, uruhare rwicyiciro cya immunotherapie icyiciro, cyane cyane nyuma yuko abarwayi bageze kuri pCR, gikomeje kuba impaka mu ivuriro.
Vuba aha, komite ngishwanama y’ibiyobyabwenge ya Oncology yo muri Amerika (FDA) yaganiriye kuri iki kibazo, ishimangira ko uruhare rwihariye rw’imiti ivura indwara rutarasobanuka neza [20]. Byaganiriweho ko: (1) Biragoye gutandukanya ingaruka za buri cyiciro cyo kuvura: kubera ko gahunda ya perioperative igizwe n'ibyiciro bibiri, neoadjuvant na adjuvant, biragoye kumenya uruhare rwa buri cyiciro kuri buri cyiciro ku ngaruka rusange, bigatuma bigorana kumenya icyiciro gikomeye, cyangwa niba ibyiciro byombi bigomba gukorwa icyarimwe; . . Mu gusubiza impaka zavuzwe haruguru, kugira ngo dushobore gufata umwanzuro usobanutse, hakenewe ibigeragezo byateguwe neza byateganijwe kugirango bigenzurwe ejo hazaza.