nkhani

Khansara ya m'mapapo yosakhala yaying'ono (NSCLC) imatenga pafupifupi 80% -85% ya chiwerengero chonse cha khansa ya m'mapapo, ndipo kuchotsa opaleshoni ndiyo njira yothandiza kwambiri yochizira kwambiri NSCLC yoyambirira. Komabe, ndi 15% yokha yochepetsera kubwereza komanso kusintha kwa 5% pazaka 5 zopulumuka pambuyo pa perioperative chemotherapy, pali chosowa chachikulu chachipatala chomwe sichinakwaniritsidwe.

Perioperative immunotherapy ya NSCLC ndi malo atsopano ofufuza m'zaka zaposachedwa, ndipo zotsatira za mayesero angapo oyendetsedwa mwachisawawa a gawo 3 akhazikitsa malo ofunikira a perioperative immunotherapy.

Immunotherapy kwa odwala omwe ali ndi khansa ya m'mapapo yosakhala yaing'ono (NSCLC) yapita patsogolo kwambiri m'zaka zaposachedwa, ndipo njira yothandizirayi sikuti imangowonjezera kupulumuka kwa odwala, komanso imapangitsa kuti moyo ukhale wabwino, ndikupereka chithandizo chothandizira pa opaleshoni yachikhalidwe.

Kutengera ndi nthawi yomwe immunotherapy imayendetsedwa, pali njira zazikulu zitatu za immunotherapy pochiza NSCLC yoyambira yoyambira:

1. Neoadjuvant immunotherapy yokha: Immunotherapy imachitidwa musanachite opaleshoni kuti achepetse kukula kwa chotupacho ndi kuchepetsa chiopsezo cha kubwereranso. Kafukufuku wa CheckMate 816 [1] adawonetsa kuti immunotherapy kuphatikiza ndi chemotherapy kumathandizira kwambiri kupulumuka popanda zochitika (EFS) mu gawo la neoadjuvant poyerekeza ndi chemotherapy yokha. Kuphatikiza apo, neoadjuvant immunotherapy imathanso kuchepetsa kuchuluka kwa kubwereza kwinaku ikuwongolera kuchuluka kwa odwala omwe ali ndi vuto lililonse (pCR), potero kuchepetsa mwayi wobwereranso pambuyo pa opaleshoni.
2. Perioperative immunotherapy (neoadjuvant + adjuvant) : Mu njira iyi, immunotherapy imayendetsedwa isanayambe kapena itatha opaleshoni kuti iwonjezere mphamvu yake ya antitumor ndikuchotsanso zotsalira zochepa zotsalira pambuyo pa opaleshoni. Cholinga chachikulu cha chithandizochi ndikuwongolera kupulumuka kwanthawi yayitali ndikuchiritsa odwala chotupa mwa kuphatikiza immunotherapy pagawo la neoadjuvant (pre-operative) ndi adjuvant (post-operative). Keynote 671 ndi woimira chitsanzo ichi [2]. Monga mayesero okhawo omwe amayendetsedwa mwachisawawa (RCT) omwe ali ndi EFS zabwino ndi mapeto a OS, adayesa mphamvu ya palizumab kuphatikizapo chemotherapy mu perioperatively resectable stage Ⅱ, ⅢA, ndi ⅢB (N2) NSCLC odwala. Poyerekeza ndi mankhwala amphamvu okha, pembrolizumab pamodzi ndi chemotherapy anawonjezera EFS yapakati ndi zaka 2.5 ndikuchepetsa chiopsezo cha matenda, kubwereranso, kapena imfa ndi 41%; KEYNOTE-671 inalinso kafukufuku woyamba wa immunotherapy kuwonetsa kupulumuka kwathunthu (OS) mu NSCLC yokhazikika, ndikuchepetsa 28% pachiwopsezo cha imfa (HR, 0.72), chochitika chofunikira kwambiri mu neoadjuvant ndi adjuvant immunotherapy pakugwiritsa ntchito koyambirira kwa NSCLC.

3. Adjuvant immunotherapy yekha: Mu njira iyi, odwala sanalandire chithandizo chamankhwala asanachite opaleshoni, ndipo ma immunodrugs anagwiritsidwa ntchito pambuyo pa opaleshoni kuti ateteze kubwereza kwa zotupa zotsalira, zomwe ziri zoyenera kwa odwala omwe ali ndi chiopsezo chachikulu chobwereza. Kafukufuku wa IMpower010 adawunikira mphamvu ya postoperative adjuvant attilizumab motsutsana ndi chithandizo choyenera chothandizira odwala omwe ali ndi gawo la IB mpaka IIIA (AJCC 7th edition) NSCLC [3]. Zotsatira zake zidawonetsa kuti chithandizo chothandizira ndi attilizumab chimatalikitsa moyo wopanda matenda (DFS) mwa odwala omwe ali ndi PD-L1 omwe ali ndi vuto ⅱto ⅢA. Kuphatikiza apo, kafukufuku wa KEYNOTE-091 / PEARLS adawonetsa momwe pembrolizumab imagwirira ntchito ngati chithandizo chothandizira odwala omwe ali ndi gawo IB mpaka IIIA NSCLC [4]. Pabolizumab idatalikitsidwa kwambiri pakati pa anthu onse (HR, 0.76), yokhala ndi DFS yapakatikati ya miyezi 53.6 mu gulu la Pabolizumab ndi miyezi 42 m'gulu la placebo. M'gulu la odwala omwe ali ndi chiwerengero cha PD-L1 chotupa (TPS) ≥50%, ngakhale kuti DFS inali yaitali mu gulu la Pabolizumab, kusiyana pakati pa magulu awiriwa sikunali kofunika kwambiri chifukwa cha kukula kwachitsanzo chaching'ono, ndipo kutsatiridwa kwautali kunali kofunikira kuti atsimikizire.

Malingana ndi ngati immunotherapy ikuphatikizidwa ndi mankhwala ena kapena njira zochizira komanso njira yophatikizira, pulogalamu ya neoadjuvant immunotherapy ndi adjuvant immunotherapy ikhoza kugawidwa m'njira zitatu zotsatirazi:

1. Single immunotherapy: Mtundu uwu wa mankhwala umaphatikizapo maphunziro monga LCMC3 [5], IMpower010 [3], KEYNOTE-091 / PEARLS [4], BR.31 [6], ndi ANVIL [7], omwe amadziwika ndi kugwiritsa ntchito mankhwala amodzi a immunotherapy monga (zatsopano) adjuvant therapy.
2. Kuphatikiza kwa immunotherapy ndi chemotherapy: Maphunziro oterowo akuphatikizapo KEYNOTE-671 [2], CheckMate 77T [8], AEGEAN [9], RATIONALE-315 [10], Neotorch [11], ndi IMpower030 [12]. Maphunzirowa adayang'ana zotsatira za kuphatikiza immunotherapy ndi chemotherapy munthawi ya perioperative.
3. Kuphatikizika kwa immunotherapy ndi njira zina zothandizira: (1) Kuphatikiza ndi ma immunodrugs ena: Mwachitsanzo, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inaphatikizidwa mu NEOSTAR test [13], lymphocyte activation gene 3 (LAG-3) antibody inaphatikizidwa mu NEO, immunoglobulin ndi T-Test cell cell (TES) Mapangidwe a ITIM adaphatikizidwa mu mayeso a SKYSCRAPER 15 Maphunziro monga TIGIT antibody kuphatikiza [15] athandizira anti-chotupa chifukwa chophatikiza mankhwala oteteza chitetezo m'thupi. (2) Kuphatikizidwa ndi radiotherapy: mwachitsanzo, duvaliumab pamodzi ndi stereotactic radiotherapy (SBRT) yapangidwa kuti ipititse patsogolo chithandizo chamankhwala cha NSCLC yoyambirira [16]; (3) Kuphatikiza ndi mankhwala odana ndi angiogenic: Mwachitsanzo, kafukufuku wa EAST ENERGY [17] adafufuza zotsatira za synergistic za ramumab kuphatikizapo immunotherapy. Kufufuza kwa mitundu ingapo ya immunotherapy kukuwonetsa kuti njira yogwiritsira ntchito immunotherapy munthawi ya perioperative sikudziwika bwino. Ngakhale kuti immunotherapy yokha yasonyeza zotsatira zabwino pa chithandizo cha perioperative, kuphatikizapo chemotherapy, radiation therapy, antiangiogenic therapy, ndi zina zoletsa chitetezo cha mthupi monga CTLA-4, LAG-3, ndi TIGIT, ofufuza akuyembekeza kupititsa patsogolo mphamvu ya immunotherapy.

Palibe kutsimikiza kwa njira yoyenera ya immunotherapy ya NSCLC yoyambilira, makamaka ngati perioperative immunotherapy poyerekeza ndi neoadjuvant immunotherapy yokha, komanso ngati chithandizo chowonjezera cha adjuvant immunotherapy chingabweretse zotsatira zowonjezera, pakadali kusowa kwachindunji koyerekeza zoyeserera.
Forde et al. adagwiritsa ntchito kusanthula koyezera kuchuluka kwa mayeso kuti ayese zotsatira za mayeso oyendetsedwa mwachisawawa, ndikusintha kuchuluka kwa anthu ndi mikhalidwe ya matenda pakati pa anthu osiyanasiyana ophunzirira kuti achepetse kusokoneza kwa zinthu izi, kupanga zotsatira za CheckMate 816 [1] ndi CheckMate 77T [8] kufanana. Nthawi yotsatizana yapakatikati inali miyezi 29.5 (CheckMate 816) ndi miyezi 33.3 (CheckMate 77T), motero, kupereka nthawi yokwanira yotsatizana kuti muwone EFS ndi njira zina zofunika kwambiri.
Pakuwunika kolemera, HR wa EFS anali 0.61 (95% CI, 0.39 kwa 0.97), akuwonetsa kuti 39% yotsika chiopsezo chobwereza kapena kufa mu gulu la perioperative nabuliumab kuphatikiza chemotherapy gulu (CheckMate 77T mode) poyerekeza ndi neoadjuvant nabuliumab kuphatikiza 6 gulu la chemotherapy 8). Gulu la perioperative nebuliuzumab kuphatikiza chemotherapy gulu lidawonetsa phindu lochepa kwa odwala onse omwe ali pachiwopsezo choyambira, ndipo zotsatira zake zidawonekera kwambiri kwa odwala omwe ali ndi chotupa chochepera 1% PD-L1 mawu (49% kuchepetsa chiopsezo chobwereza kapena kufa). Kuonjezera apo, kwa odwala omwe alephera kukwaniritsa pCR, gulu la perioperative nabuliumab lophatikizana ndi chemotherapy gulu linasonyeza phindu lalikulu la EFS (35% kuchepetsa chiopsezo cha kubwereza kapena imfa) kusiyana ndi neoadjuvant nabuliumab kuphatikiza gulu la chemotherapy. Zotsatirazi zikusonyeza kuti perioperative immunotherapy model ndi yopindulitsa kuposa chitsanzo cha neoadjuvant immunotherapy chokha, makamaka kwa odwala omwe ali ndi PD-L1 otsika komanso zotsalira zotupa pambuyo pa chithandizo choyamba.
Komabe, kufananitsa kwina kosalunjika (monga kusanthula kwa meta) sikunawonetse kusiyana kwakukulu pakupulumuka pakati pa neoadjuvant immunotherapy ndi perioperative immunotherapy [18]. Kusanthula kwa meta kutengera chidziwitso cha wodwala aliyense kunapeza kuti perioperative immunotherapy ndi neoadjuvant immunotherapy zinali ndi zotsatira zofanana pa EFS m'magulu onse a pCR ndi omwe si a PCR mwa odwala omwe ali ndi NSCLC yoyambirira [19]. Kuphatikiza apo, chopereka cha adjuvant immunotherapy gawo, makamaka odwala atapeza pCR, amakhalabe mkangano m'chipatala.
Posachedwapa, US Food and Drug Administration (FDA) Oncology Drug Advisory Committee yakambirana za nkhaniyi, ndikugogomezera kuti gawo la adjuvant immunotherapy silikudziwikabe [20]. Zinakambidwa kuti: (1) N'zovuta kusiyanitsa zotsatira za gawo lililonse la chithandizo: chifukwa pulogalamu ya perioperative imakhala ndi magawo awiri, neoadjuvant ndi adjuvant, n'zovuta kudziwa momwe munthu aliyense payekha amathandizira gawo lililonse pazochitika zonse, zomwe zimapangitsa kuti zikhale zovuta kudziwa kuti ndi gawo liti lomwe ndi lofunika kwambiri, kapena ngati magawo awiriwa ayenera kuchitidwa panthawi imodzi; (2) Kuthekera kwa kuwonjezereka: ngati immunotherapy ikuphatikizidwa m'zigawo zonse za chithandizo, zingayambitse odwala kulandira mankhwala osokoneza bongo ndikuwonjezera chiopsezo cha zotsatirapo; (3) Kuwonjezeka kwa mankhwala ochizira: Chithandizo choonjezera mu gawo la chithandizo cha adjuvant chingayambitse kulemedwa kwakukulu kwa mankhwala kwa odwala, makamaka ngati pali kusatsimikizika pa zomwe zimathandizira kuti zikhale zogwira mtima. Poyankha mkangano womwe uli pamwambapa, kuti tipeze yankho lomveka bwino, mayesero opangidwa mwachisawawa amafunikira kuti atsimikizidwenso m'tsogolomu.