iindaba

Umhlaza wemiphunga weseli engeyiyo encinci (NSCLC) uthatha malunga ne-80% -85% yenani lilonke lomhlaza wemiphunga, kwaye uqhaqho loqhaqho yeyona ndlela isebenzayo yonyango olukhawulezayo lwe-NSCLC yokuqala. Nangona kunjalo, nge-15% kuphela yokunciphisa ukuphindaphinda kunye nokuphuculwa kwe-5% kwiminyaka emi-5 yokusinda emva kwe-chemotherapy ye-perioperative, kukho imfuno enkulu yeklinikhi engafezekanga.

I-Perioperative immunotherapy ye-NSCLC yindawo entsha yophando kwiminyaka yakutshanje, kwaye iziphumo zenani leemvavanyo ezilawulwa ngokungenamkhethe ze-3 ziye zaseka indawo ebalulekileyo ye-perioperative immunotherapy.

Immunotherapy kwizigulana ezinomhlaza wemiphunga weseli engeyiyo encinci (NSCLC) yenze inkqubela phambili enkulu kwiminyaka yakutshanje, kwaye esi sicwangciso sonyango asigcini nje ukwandisa ukusinda kwezigulana, kodwa siphucula umgangatho wobomi, sibonelela ngesongezelelo esisebenzayo kuqhaqho lwemveli.

Kuxhomekeka xa i-immunotherapy ilawulwa, kukho iipateni ezintathu eziphambili ze-immunotherapy kunyango lwe-NSCLC esebenzayo:

1. I-Neoadjuvant immunotherapy yodwa: I-Immunotherapy yenziwa ngaphambi kokuhlinzwa ukunciphisa ubukhulu be-tumor kunye nokunciphisa umngcipheko wokuphindaphinda. Uphononongo lwe-CheckMate 816 [1] lubonise ukuba unyango lwe-immunotherapy oludityaniswe nechemotherapy luphucule kakhulu ukusinda kwesiganeko (EFS) kwisigaba se-neoadjuvant xa kuthelekiswa nechemotherapy yodwa. Ukongeza, i-neoadjuvant immunotherapy inokunciphisa izinga lokuphindaphinda ngelixa iphucula izinga lokuphendula elipheleleyo le-pathological (pCR) yezigulane, ngaloo ndlela inciphisa amathuba okuphindaphinda emva kokuhlinzwa.
2. I-Perioperative immunotherapy (i-neoadjuvant + i-adjuvant) : Kule ndlela, i-immunotherapy ilawulwa ngaphambi nangemva kokuhlinzwa ukuze kwandiswe impembelelo yayo ye-antitumor kwaye isuse ngakumbi izilonda ezincinci eziseleyo emva kokuhlinzwa. Injongo ephambili yale modeli yonyango kukuphucula ukusinda kwexesha elide kunye namazinga okunyanga izigulane ze-tumor ngokudibanisa i-immunotherapy kwi-neoadjuvant (pre-operative) kunye ne-adjuvant (post-operative) izigaba. Inqaku eliphambili 671 ngummeli wale modeli [2]. Njengolulingo kuphela olulawulwa ngokungahleliwe (RCT) olune-EFS elungileyo kunye ne-OS endpoints, ivavanye ukusebenza kwe-palizumab edityaniswe nechemotherapy kwinqanaba leperioperatively rectable Ⅱ, ⅢA, kunye ⅢB (N2) izigulane ze-NSCLC. Xa kuthelekiswa ne-chemotherapy yodwa, i-pembrolizumab idibene ne-chemotherapy yandisa i-EFS ephakathi nge-2.5 iminyaka kwaye yanciphisa umngcipheko wokuqhubela phambili kwesifo, ukuphindaphinda, okanye ukufa nge-41%; I-KEYNOTE-671 yayiyeyokuqala isifundo se-immunotherapy ukubonisa inzuzo yokusinda (OS) kwi-NSCLC ehlaziywayo, kunye nokunciphisa i-28% kumngcipheko wokufa (HR, 0.72), isiganeko esibalulekileyo kwi-neoadjuvant kunye ne-adjuvant immunotherapy kwi-NSCLC esebenzayo.

3. I-Adjuvant immunotherapy yodwa: Kule ndlela, izigulane azizange zifumane unyango lweziyobisi ngaphambi kokuhlinzwa, kwaye i-immunodrugs isetyenziswe emva kokuhlinzwa ukukhusela ukuphindaphinda kwezicubu ezishiyekileyo, ezifanelekileyo kwizigulane ezinomngcipheko ophezulu wokuphindaphinda. Uphononongo lwe-IMpower010 luvavanye ukuphumelela kwe-postoperative adjuvant attilizumab ngokubhekiselele kunyango olululo lwenkxaso kwizigulane ezine-IB ukuya kwi-IIA (AJCC 7th edition) NSCLC [3]. Iziphumo zibonise ukuba unyango olongezelelweyo kunye ne-attilizumab landisa ngokubalulekileyo ukusinda okungenasifo (DFS) kwi-PD-L1 izigulana ezilungileyo kwinqanaba ⅱukuya ku-ⅢA. Ukongeza, uphando lwe-KEYNOTE-091 / PEARLS luvavanye isiphumo se-pembrolizumab njengonyango oluncedisayo kwizigulana ezichane ngokupheleleyo ezinenqanaba le-IB ukuya kwi-IIA NSCLC [4]. I-Pabolizumab yandiswa kakhulu kuluntu lonke (HR, 0.76), kunye ne-DFS ephakathi kweenyanga ze-53.6 kwiqela le-Pabolizumab kunye neenyanga ze-42 kwiqela le-placebo. Kwiqela elincinane lezigulane ezine-PD-L1 i-tumor proportion score (TPS) ≥50%, nangona i-DFS yandiswe ixesha elide kwiqela le-Pabolizumab, umahluko phakathi kwamaqela amabini awubalulekanga ngokwezibalo ngenxa yobukhulu besampulu encinci, kwaye ulandelelwano olude lwalufuneka ukuze kuqinisekiswe.

Ngokumalunga nokuba i-immunotherapy idityaniswe namanye amachiza okanye amanyathelo onyango kunye nemo yodibaniso, inkqubo ye-neoadjuvant immunotherapy kunye ne-adjuvant immunotherapy inokwahlulwa kwezi ndlela zintathu zilandelayo:

1. I-immunotherapy eyodwa: Olu hlobo lonyango lubandakanya izifundo ezifana ne-LCMC3 [5], IMpower010 [3], KEYNOTE-091 / PEARLS [4], BR.31 [6], kunye ne-ANVIL [7], ebonakaliswe ngokusetyenziswa kweziyobisi ze-immunotherapy enye njenge (entsha) unyango lwe-adjuvant.
2. Ukudibanisa i-immunotherapy kunye ne-chemotherapy: Izifundo ezinjalo ziquka i-KEYNOTE-671 [2], i-CheckMate 77T [8], i-AEGEAN [9], i-RATIONALE-315 [10], i-Neotorch [11], kunye ne-IMpower030 [12]. Ezi zifundo zijonge iziphumo zokudibanisa i-immunotherapy kunye ne-chemotherapy kwixesha le-perioperative.
3. Ukudibanisa i-immunotherapy kunye nezinye iindlela zonyango: (1) Ukudibanisa kunye nezinye i-immunodrugs: Ngokomzekelo, i-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) idibaniswe kuvavanyo lwe-NEOSTAR [13], i-lymphocyte activation gene 3 (LAG-3) i-antibody yadibaniswa kwi-NEOglobu kunye ne-Test cell cell ye-TEO-Predi Izakhiwo ze-ITIM zadityaniswa kwi-SKYSCRAPER 15 test Studies ezifana ne-TIGIT antibody indibaniselwano [15] ziye zaphucula umphumo wokuchasana ne-tumor ngokudibanisa amachiza omzimba. (2) Idityaniswe ne-radiotherapy: umzekelo, i-duvaliumab idibene ne-stereotactic radiotherapy (SBRT) yenzelwe ukunyusa umphumo wonyango we-NSCLC yokuqala [16]; (3) Ukudibanisa kunye neziyobisi ezichasene ne-angiogenic: Ngokomzekelo, isifundo se-ESTERS ENERGY [17] sihlolisise umphumo we-synergistic we-ramumab edibene ne-immunotherapy. Ukuphononongwa kweendlela ezininzi ze-immunotherapy kubonisa ukuba indlela yokusetyenziswa kwe-immunotherapy kwixesha le-perioperative ayikaqondwa ngokupheleleyo. Nangona i-immunotherapy yodwa ibonise iziphumo ezilungileyo kunyango lwe-perioperative, ngokudibanisa i-chemotherapy, unyango lwe-radiation, unyango lwe-antiangiogenic, kunye nezinye i-immune checkpoint inhibitors ezifana ne-CTLA-4, i-LAG-3, kunye ne-TIGIT, abaphandi banethemba lokuphucula ngakumbi ukusebenza kwe-immunotherapy.

Akukabikho sigqibo malunga neyona ndlela ilungileyo yonyango lwe-immunotherapy esebenzayo ekuqaleni kwe-NSCLC, ngakumbi ukuba i-perioperative immunotherapy xa ithelekiswa ne-neoadjuvant immunotherapy iyodwa, kwaye nokuba i-adjuvant immunotherapy eyongezelelweyo inokuzisa iziphumo ezibalulekileyo ezongezelelweyo, kusekho ukunqongophala kweziphumo zolingo oluthe ngqo.
Forde et al. kusetyenziswe uhlalutyo lwe-propensity yokuhlola ukulinganisa ukulinganisa umphumo wezilingo ezilawulwa ngokungenamkhethe, kwaye ulungelelanise i-demographics esisiseko kunye neempawu zesifo phakathi kwabantu abahlukeneyo bokufunda ukunciphisa umphumo ophazamisayo wale miba, okwenza iziphumo ze-CheckMate 816 [1] kunye ne-CheckMate 77T [8] zithelekiseke ngakumbi. Ixesha lokulandelela eliphakathi laliyienyanga ze-29.5 (CheckMate 816) kunye neenyanga ze-33.3 (CheckMate 77T), ngokulandelanayo, ukubonelela ixesha elaneleyo lokulandela ukujonga i-EFS kunye nezinye iindlela eziphambili zokusebenza.
Kuhlalutyo olulinganisiweyo, i-HR ye-EFS yayingu-0.61 (95% CI, 0.39 ukuya kwi-0.97), ebonisa ukuba i-39% iphantsi komngcipheko wokuphindaphinda okanye ukufa kwiqela le-perioperative nabuliumab edibeneyo ye-chemotherapy (i-CheckMate 77T mode) xa kuthelekiswa ne-neoadjuvant nabuliumab edibeneyo ye-chemotherapy group1 (Check6 i-chemotherapy group1). I-perioperative nebuliuzumab kunye neqela le-chemotherapy libonise inzuzo ethobekileyo kuzo zonke izigulane kwinqanaba lokuqala, kwaye umphumo wawuchazwe ngakumbi kwizigulane ezineenkcazo ezingaphantsi kwe-1% ye-tumor PD-L1 (49% yokunciphisa umngcipheko wokuphindaphinda okanye ukufa). Ukongezelela, kwizigulane ezingazange ziphumelele ukufezekisa i-pCR, i-perioperative nabuliumab edibeneyo ye-chemotherapy group ibonise inzuzo enkulu ye-EFS (i-35% yokunciphisa umngcipheko wokuphindaphinda okanye ukufa) kune-neoadjuvant nabuliumab edibeneyo neqela le-chemotherapy. Ezi ziphumo zibonisa ukuba imodeli ye-perioperative immunotherapy iluncedo ngakumbi kunemodeli ye-neoadjuvant immunotherapy yodwa, ngakumbi kwizigulana ezinenkcazo ephantsi ye-PD-L1 kunye neentsalela zethumba emva konyango lokuqala.
Nangona kunjalo, uthelekiso oluthile olungathanga ngqo (olufana nohlalutyo lwe-meta) alubonisanga mahluko ubalulekileyo ekusindeni phakathi kwe-neoadjuvant immunotherapy kunye ne-perioperative immunotherapy [18]. Uhlalutyo lwe-meta olusekwe kwidatha yesigulana ngasinye yafumanisa ukuba i-perioperative immunotherapy kunye ne-neoadjuvant immunotherapy ineziphumo ezifanayo kwi-EFS kuwo omabini amacandelwana e-pCR kunye ne-non-PCR kwizigulana ezine-NSCLC esebenzayo [19]. Ukongezelela, igalelo lesigaba se-adjuvant immunotherapy, ngakumbi emva kokuba izigulane ziphumelele i-pCR, zihlala ziphikisana neklinikhi.
Kutshanje, i-US Food and Drug Administration (FDA) ye-Oncology Drug Advisory Committee yaxoxa ngalo mbandela, igxininisa ukuba indima ethile ye-adjuvant immunotherapy ayikacaci [20]. Kwaxutyushwa ukuba: (1) Kunzima ukuhlukanisa imiphumo yesigaba ngasinye sonyango: ngenxa yokuba inkqubo ye-perioperative iqukethe izigaba ezibini, i-neoadjuvant kunye ne-adjuvant, kunzima ukugqiba igalelo lomntu ngamnye kwisigaba ngasinye kwisiphumo esipheleleyo, okwenza kube nzima ukucacisa ukuba yiyiphi isigaba esibaluleke kakhulu, okanye ukuba zombini izigaba kufuneka ziqhutywe ngaxeshanye; (2) Inokwenzeka yokuxhatshazwa: ukuba i-immunotherapy ibandakanyeka kuzo zombini izigaba zonyango, kunokubangela ukuba izigulane zithole unyango olugqithisileyo kunye nokwandisa umngcipheko wemiphumo emibi; (3) Ukunyuka komthwalo wonyango: Unyango olongezelelweyo kwisigaba sonyango lwe-adjuvant lungakhokelela kumthwalo ophezulu wonyango kwizigulane, ngakumbi ukuba kukho ukungaqiniseki malunga negalelo layo ekusebenzeni ngokubanzi. Ukuphendula le ngxoxo-mpikiswano ingentla, ukuze wenze isigqibo esicacileyo, iimvavanyo ezilawulwa ngokungqongqo eziyilwe ngokungenamkhethe ziyafuneka ukuze kuqinisekiswe ngakumbi kwixesha elizayo.