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Isiri diki-diki kenza yemapapu (NSCLC) inoita 80% -85% yehuwandu hwekenza yemapapu, uye kuvhiya kuvhiya ndiyo nzira inoshanda kwazvo yekurapa kwakanyanya kwekutanga NSCLC. Nekudaro, nekungodzikiswa kwegumi neshanu muzana mukudzoka uye kuvandudzwa kwe5% mukurarama kwemakore mashanu mushure me perioperative chemotherapy, pane chinodikanwa chikuru chekiriniki chisina kukwana.

Perioperative immunotherapy yeNSCLC inzvimbo nyowani yekutsvagisa mumakore achangopfuura, uye mhedzisiro yehuwandu hwechikamu che3 randomized controlled trials yakasimbisa chinzvimbo chakakosha cheperioperative immunotherapy.

Immunotherapy yevarwere vane operationable yekutanga nhanho isiri-diki cell yemapapu cancer (NSCLC) yakafambira mberi zvakanyanya mumakore achangopfuura, uye nzira yekurapa iyi haingowedzere hupenyu hwevarwere chete, asi zvakare inovandudza hupenyu, ichipa chinowedzera chinoshanda mukuvhiya kwechinyakare.

Zvichienderana nekuti immunotherapy inoitiswa riinhi, kune matatu makuru mapatani e immunotherapy mukurapa kunoshanda kwekutanga-nhanho NSCLC:

1. Neoadjuvant immunotherapy chete: Immunotherapy inoitwa vasati vavhiyiwa kuderedza ukuru hwebundu uye kuderedza dambudziko rekudzokazve. Chidzidzo cheCheckMate 816 [1] chakaratidza kuti immunotherapy yakasanganiswa nechemotherapy yakanyanya kunatsiridza kusapona kwechiitiko (EFS) muchikamu cheneoadjuvant kana ichienzaniswa nechemotherapy chete. Pamusoro pezvo, neoadjuvant immunotherapy inogona zvakare kuderedza chiyero chekudzokorora uku ichivandudza pathological yakakwana yekupindura mwero (pCR) yevarwere, nekudaro ichidzikisa mukana wekudzoka kwepashure.
2. Perioperative immunotherapy (neoadjuvant + adjuvant) : Muchiitiko ichi, immunotherapy inoshandiswa mushure mekuvhiyiwa kuti iwedzere maitiro ayo antitumor uye kuwedzera kubvisa zviduku zvakasara mushure mekuvhiyiwa. Chinangwa chikuru cheiyi modhi yekurapa ndechekuvandudza kurarama kwenguva refu uye kurapa mareti evarwere vebundu nekubatanidza immunotherapy paneoadjuvant (pre-operative) uye adjuvant (post-operative) nhanho. Keynote 671 mumiriri weiyi modhi [2]. Seye chete muyedzo wakasarudzika (RCT) une EFS yakanaka uye OS endpoints, yakaongorora kushanda kwepalizumab yakasanganiswa nechemotherapy muperioperatively rectable stage Ⅱ, ⅢA, uye ⅢB (N2) NSCLC varwere. Kuenzaniswa nekemotherapy chete, pembrolizumab yakasanganiswa nekemotherapy yakawedzera EFS yepakati nemakore 2.5 uye yakaderedza ngozi yekuwedzera kwechirwere, kudzokazve, kana kufa ne41%; KEYNOTE-671 yaive zvakare yekutanga immunotherapy kudzidza kuratidza kupona kwese (OS) kubatsirwa muNSCLC inogoneka, ine kuderedzwa kwe28% munjodzi yerufu (HR, 0.72), chiitiko chakakosha muNeoadjuvant uye adjuvant immunotherapy yekushandisa yekutanga-nhanho NSCLC.

3. Adjuvant immunotherapy chete: Muchiitiko ichi, varwere havana kugamuchira kurapwa kwezvinodhaka vasati vavhiyiwa, uye immunodrugs yakashandiswa mushure mekuvhiyiwa kudzivirira kudzoka kwezvipembenene zvakasara, izvo zvakakodzera kune varwere vane ngozi yekudzoka zvakare. The IMpower010 chidzidzo chakaongorora kushanda kwepostoperative adjuvant attilizumab maringe nerapirwo yakakwana yekutsigira muvarwere vane danho rakanyatsogadziriswa IB kusvika IIIA (AJCC 7th edition) NSCLC [3]. Mhedzisiro yacho yakaratidza kuti adjunct therapy neattilizumab yakanyanya kurebesa hurwere-isina kupona (DFS) muPD-L1 vakanaka varwere padanho ⅱ kusvika ⅢA. Mukuwedzera, iyo KEYNOTE-091 / PEARLS chidzidzo chakaongorora mhedzisiro yepembrolizumab seye adjunctive therapy muvarwere vakanyatsogadziriswa vane nhanho IB kusvika IIIA NSCLC [4]. Pabolizumab yakawedzera kurebesa muhuwandu hwese (HR, 0.76), ine yepakati DFS yemwedzi 53.6 muboka rePabolizumab uye 42 mwedzi muboka re placebo. Muchikamu chiduku chevarwere vane PD-L1 tumor proportion score (TPS) ≥50%, kunyange zvazvo DFS yakarebeswa muboka rePabolizumab, musiyano pakati pemapoka maviri acho hauna kunyanya kukosha nekuda kwekukura kwemuenzaniso muduku, uye kutevera kwenguva refu kwaidiwa kusimbisa.

Zvinoenderana nekuti immunotherapy inosanganiswa nemimwe mishonga kana nzira dzekurapa uye nzira yekubatanidza, chirongwa che neoadjuvant immunotherapy uye adjuvant immunotherapy chinogona kukamurwa kuva matatu anotevera modhi:

1. Single immunotherapy: Rudzi urwu rwekurapa runosanganisira zvidzidzo zvakadai seLCMC3 [5], IMpower010 [3], KEYNOTE-091 / PEARLS [4], BR.31 [6], uye ANVIL [7], inoratidzwa nekushandiswa kwemishonga imwe chete yeimmunotherapy se (itsva) adjuvant therapy.
2. Kusanganiswa kwe immunotherapy uye chemotherapy: Zvidzidzo zvakadaro zvinosanganisira KEYNOTE-671 [2], CheckMate 77T [8], AEGEAN [9], RATIONALE-315 [10], Neotorch [11], uye IMpower030 [12]. Zvidzidzo izvi zvakatarisa mhedzisiro yekubatanidza immunotherapy uye chemotherapy munguva yeperioperative.
3. Kusanganiswa kwe immunotherapy nemamwe maitiro ekurapa: (1) Kusanganiswa nemamwe immunodrugs: Somuenzaniso, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) yakabatanidzwa mu NEOSTAR test [13], lymphocyte activation gene 3 (LAG-3) antibody yakabatanidzwa mu NEOglong-Cell-Predilin, immunoglobu uye T-Test 1. Zvimiro zveITIM zvakasanganiswa muSKYSCRAPER 15 bvunzo Zvidzidzo zvakaita seTIGIT antibody musanganiswa [15] zvakasimudzira anti-tumor mhedzisiro kuburikidza nekusanganiswa kwemishonga yekudzivirira. (2) Yakasanganiswa neradiotherapy: semuenzaniso, duvaliumab yakasanganiswa ne stereotactic radiotherapy (SBRT) yakagadzirirwa kusimudzira maitiro ekurapa kwekutanga NSCLC [16]; (3) Kusanganiswa nemishonga inorwisa-angiogenic: Semuenzaniso, iyo EAST ENERGY kudzidza [17] yakaongorora synergistic mhedzisiro yeramumab yakasanganiswa ne immunotherapy. Kuongorora kweakawanda immunotherapy modhi kunoratidza kuti mashandisiro ekushandisa immunotherapy munguva yeperioperative haisati yanyatsonzwisiswa. Kunyange zvazvo immunotherapy chete yakaratidza migumisiro yakanaka mukurapa kweperioperative, nekubatanidza chemotherapy, radiation therapy, antiangiogenic therapy, uye mamwe immune checkpoint inhibitors akadai seCTLA-4, LAG-3, uye TIGIT, vatsvakurudzi vanotarisira kuwedzera kuwedzera kushanda kwe immunotherapy.

Hapasati pasisina mhedziso pamusoro peiyo yakakwana modhi ye immunotherapy yekushandisa yekutanga NSCLC, kunyanya ingave perioperative immunotherapy kana ichienzaniswa neoadjuvant immunotherapy chete, uye kana imwe adjuvant immunotherapy inogona kuunza yakakosha mimwe mhedzisiro, pachine kushomeka kwekuenzanisa kwakananga mhedzisiro.
Forde et al. yakashandisa kuongororwa kwemaitiro ekuyera kuyerwa kwekuongorora kutevedzera maitiro ezviyedzo zvakadzorwa zvisina kurongeka, uye kugadzirisa huwandu hwekutanga hwehuwandu hwevanhu uye hunhu hwechirwere pakati pehuwandu hwekudzidza hwakasiyana-siyana kuti kuderedze kuvhiringika kwezvinhu izvi, zvichiita kuti mhedzisiro yeCheckMate 816 [1] uye CheckMate 77T [8] ienzane. Nguva yekutevera yepakati yaive mwedzi 29.5 (CheckMate 816) uye 33.3 mwedzi (CheckMate 77T), zvichiteerana, ichipa nguva yakawanda yekutevera yekucherechedza EFS uye mamwe matanho akakosha ekubudirira.
Mukuongorora kwakayerwa, HR yeEFS yaive 0.61 (95% CI, 0.39 kusvika 0.97), zvichiratidza kuti 39% yakaderera njodzi yekudzokazve kana kufa muperioperative nabuliumab yakasanganiswa chemotherapy boka (CheckMate 77T mode) ichienzaniswa neiyo neoadjuvant nabuliumab yakasanganiswa chemotherapy boka18. Iyo perioperative nebuliuzumab plus chemotherapy boka yakaratidza kubatsirwa zvine mwero kune vese varwere padanho rekutanga, uye mhedzisiro yacho yainyanya kutaurwa kune varwere vane isingasviki 1% bundu PD-L1 kutaura (49% kuderedzwa kwenjodzi yekudzokazve kana kufa). Mukuwedzera, kune varwere vakakundikana kuwana pCR, perioperative nabuliumab yakasanganiswa chemotherapy boka yakaratidza kubatsirwa kukuru kweEFS (35% kuderedza mungozi yekudzokazve kana kufa) kupfuura neoadjuvant nabuliumab yakasanganiswa chemotherapy boka. Mhedzisiro iyi inoratidza kuti iyo perioperative immunotherapy modhi inobatsira kupfuura iyo neoadjuvant immunotherapy modhi chete, kunyanya muvarwere vane yakaderera PD-L1 kutaura uye bundu rasara mushure mekutanga kurapwa.
Zvisinei, kumwe kuenzanisa kusina kunanga (kwakadai se-meta-analyses) hakuna kuratidza musiyano mukuru mukupona pakati neoadjuvant immunotherapy uye perioperative immunotherapy [18]. Meta-analysis yakavakirwa pane mumwe murwere data yakawana kuti perioperative immunotherapy uye neoadjuvant immunotherapy yaive nemhedzisiro yakafanana paEFS mune ese pCR uye asiri-PCR subgroups mune varwere vane operable-danho rekutanga NSCLC [19]. Uye zvakare, mupiro weiyo adjuvant immunotherapy chikamu, kunyanya mushure mekunge varwere vawana pCR, inoramba iine gakava mukiriniki.
Munguva pfupi yapfuura, US Food and Drug Administration (FDA) Oncology Drugs Advisory Committee yakakurukura nyaya iyi, ichisimbisa kuti basa chairo readjuvant immunotherapy harisati ranyatsojeka [20]. Yakakurukurwa kuti: (1) Zvakaoma kusiyanisa migumisiro yechikamu chimwe nechimwe chekurapa: nokuti chirongwa cheperioperative chinosanganisira zvikamu zviviri, neoadjuvant uye adjuvant, zvakaoma kuziva mupiro wega wega wechikamu chimwe nechimwe kusvika kune chiitiko chose, zvichiita kuti zvive zvakaoma kuziva kuti ndechipi chikamu chinonyanya kukosha, kana kuti zvikamu zviviri zvinofanira kuitwa panguva imwe chete; (2) Mukana wekuwedzera: kana immunotherapy inobatanidzwa muzvikamu zviviri zvekurapa, zvinogona kuita kuti varwere vagamuchire zvakanyanya uye kuwedzera njodzi yemigumisiro; (3) Kuwedzerwa mutoro wekurapa: Kuwedzerwa kurapwa muchikamu chekurapa kweadjuvant kunogona kutungamirira kune mutoro wepamusoro wekurapa kune varwere, kunyanya kana pane kusava nechokwadi pamusoro pekubatsira kwayo pakubudirira kwese. Mukupindura kune gakava riri pamusoro, kuti tiwane mhedziso yakajeka, zvakaomesesa zvakagadziridzwa zviedzo zvinodzorwa zvinodikanwa kuti tive nechokwadi mune ramangwana.