ozi

Ọrịa cancer akpa ume na-abụghị obere cell (NSCLC) bụ ihe dị ka 80%-85% nke ọnụ ọgụgụ ọrịa cancer akpa ume, na ịwa ahụ bụ ụzọ kachasị dị irè maka ọgwụgwọ radical nke mmalite NSCLC. Agbanyeghị, na naanị mbelata 15% na nlọghachite yana mmụba 5% na ndụ afọ 5 mgbe chemotherapy gachara, enwere nnukwu mkpa ụlọ ọgwụ na-emezughị.

Immunotherapy Perioperative maka NSCLC bụ ebe nyocha ọhụrụ n'ime afọ ndị na-adịbeghị anya, yana nsonaazụ nke ọnụọgụ nke usoro 3 nke a na-achịkwaghị achịkwa eguzobewo ọnọdụ dị mkpa nke immunotherapy perioperative.

Immunotherapy maka ndị ọrịa nwere ọrịa cancer akpa ume na-abụghị obere cell (NSCLC) enweela ọganihu dị ukwuu n'afọ ndị na-adịbeghị anya, na usoro ọgwụgwọ a ọ bụghị nanị na-agbatị ndụ nke ndị ọrịa, kamakwa ọ na-eme ka ndụ dịkwuo mma, na-enye mgbakwunye dị irè na ịwa ahụ omenala.

Dabere na mgbe a na-enye immunotherapy, enwere usoro atọ bụ isi nke immunotherapy na ọgwụgwọ nke NSCLC n'oge na-arụ ọrụ:

1. Neoadjuvant immunotherapy naanị: A na-eme ọgwụgwọ immunotherapy tupu ịwa ahụ iji belata nha etuto ahụ ma belata ihe ize ndụ nke nlọghachi. Nnyocha CheckMate 816 [1] gosiri na immunotherapy jikọtara ya na chemotherapy kwalitere nlanarị na-enweghị mmemme (EFS) na usoro neoadjuvant ma e jiri ya tụnyere chemotherapy naanị. Tụkwasị na nke ahụ, neoadjuvant immunotherapy nwekwara ike ibelata nlọghachi azụ mgbe ọ na-eme ka ọnụọgụ nzaghachi zuru ezu nke pathological (pCR) nke ndị ọrịa, si otú a na-ebelata ohere nke nlọghachi azụ.
2. Perioperative immunotherapy (neoadjuvant + adjuvant): N'ime ọnọdụ a, a na-enye immunotherapy tupu ịwa ahụ na mgbe a gwọchara ya iji mee ka mmetụta antitumor dịkwuo elu ma wepụkwa ọnya dị ntakịrị mgbe ịwachara ahụ. Ebumnuche bụ isi nke ụdị ọgwụgwọ a bụ imeziwanye ndụ ogologo oge na ọgwụgwọ ọnụego maka ndị ọrịa etuto ahụ site na ijikọta immunotherapy na neoadjuvant (tupu arụ ọrụ) na adjuvant (post-operative) nkebi. Isi igodo 671 bụ nnọchite anya ihe nlereanya a [2]. Dị ka naanị ule a na-achịkwa nke na-enweghị usoro (RCT) nwere ezigbo EFS na njedebe OS, ọ tụlere ịdị irè nke palizumab jikọtara ya na chemotherapy na ọkwa nke nwere ike imegharị Ⅱ, ⅢA, na ⅢB (N2) ndị ọrịa NSCLC. E jiri ya tụnyere chemotherapy naanị, pembrolizumab jikọtara ya na chemotherapy gbatịpụrụ etiti EFS site na afọ 2.5 ma belata ihe ize ndụ nke ọganihu ọrịa, nlọghachi, ma ọ bụ ọnwụ site na 41%; KEYNOTE-671 bụkwa ihe ọmụmụ immunotherapy mbụ iji gosipụta uru nlanarị (OS) na NSCLC resectable, yana mbelata 28% n'ihe ize ndụ nke ọnwụ (HR, 0.72), ihe dị ịrịba ama na neoadjuvant na adjuvant immunotherapy maka NSCLC na-arụ ọrụ n'oge mbụ.

3. Adjuvant immunotherapy naanị: N'ọnọdụ a, ndị ọrịa anaghị enweta ọgwụgwọ ọgwụ tupu ịwa ahụ, a na-ejikwa immunodrugs mgbe a wachara ya ahụ iji gbochie nlọghachi nke etuto ahụ fọdụrụnụ, nke dabara maka ndị ọrịa nwere nnukwu ihe ize ndụ nlọghachi. Ọmụmụ ihe IMpower010 tụlere ịdị irè nke adjuvant adjuvant attilizumab na ọgwụgwọ nkwado kachasị mma na ndị ọrịa nwere ọkwa IB na IIIA (mbipụta AJCC 7th) NSCLC [3]. Nsonaazụ gosiri na ọgwụgwọ mgbakwunye na attilizumab na-adị ogologo ndụ na-enweghị ọrịa (DFS) na ndị ọrịa PD-L1 dị mma na ọkwa ⅱto ⅢA. Tụkwasị na nke ahụ, nchọpụta KEYNOTE-091/PEARLS tụlere mmetụta nke pembrolizumab dị ka ọgwụgwọ mgbakwunye na ndị ọrịa gbapụrụ kpamkpam na ọkwa IB ruo IIIA NSCLC [4]. Pabolizumab gbatịrị ogologo oge na ọnụ ọgụgụ mmadụ niile (HR, 0.76), yana DFS etiti nke ọnwa 53.6 n'ime otu Pabolizumab na ọnwa 42 na otu placebo. Na ngalaba nke ndị ọrịa nwere PD-L1 tumor proportion score (TPS) ≥50%, ọ bụ ezie na DFS na-agbatị ogologo oge n'ime ìgwè Pabolizumab, ọdịiche dị n'etiti ìgwè abụọ ahụ abụghị ihe ndekọ ọnụ ọgụgụ n'ihi obere ihe nlele, na ogologo oge dị mkpa iji kwado ya.

Dabere na ma ejikọtara immunotherapy na ọgwụ ndị ọzọ ma ọ bụ usoro ọgwụgwọ yana ụdị nchikota, enwere ike kewaa mmemme nke neoadjuvant immunotherapy na adjuvant immunotherapy n'ime ụzọ atọ ndị a:

1. Single immunotherapy: Ụdị ọgwụgwọ a gụnyere ọmụmụ ihe dị ka LCMC3 [5], IMpower010 [3], KEYNOTE-091/PEARLS [4], BR.31 [6], na ANVIL [7], nke ejiri otu ọgwụ immunotherapy eme ihe dị ka (ọhụrụ) ọgwụgwọ adjuvant.
2. Nchikota nke immunotherapy na chemotherapy: Ọmụmụ ihe dị otú ahụ gụnyere KEYNOTE-671 [2], CheckMate 77T [8], AEGEAN [9], RATIONALE-315 [10], Neotorch [11], na IMpower030 [12]. Ọmụmụ ihe ndị a lere anya mmetụta nke ijikọta immunotherapy na chemotherapy n'ime oge perioperative.
3. Nchikota nke immunotherapy na ndị ọzọ ụdị ọgwụgwọ: (1) Nchikota na ndị ọzọ immunodrugs: Dị ka ihe atụ, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) jikọtara na NEOSTAR ule [13], lymphocyte activation gene 3 (LAG-3) antibody e jikọtara na NEO-Predict-Lung, na cell IT bụ ihe ejikọtara na IM. Nnwale SKYSCRAPER 15 Nnyocha dị ka TIGIT antibody ngwakọta [15] emeela ka mmetụta mgbochi tumor dịkwuo mma site na nchikota ọgwụ mgbochi. (2) Ejikọtara ya na ọgwụgwọ redio: dịka ọmụmaatụ, duvaliumab jikọtara ya na stereotactic radiotherapy (SBRT) emebere iji kwalite mmetụta ọgwụgwọ nke NSCLC n'oge [16]; (3) Ngwakọta na ọgwụ mgbochi angiogenic: Dịka ọmụmaatụ, ọmụmụ EAST ENERGY [17] nyochara mmetụta synergistic nke ramumab jikọtara na immunotherapy. Nchọgharị nke ọtụtụ ụdị immunotherapy na-egosi na usoro ngwa nke immunotherapy n'oge perioperative ka amabeghị nke ọma. Ọ bụ ezie na immunotherapy naanị egosila nsonaazụ dị mma na ọgwụgwọ perioperative, site na ijikọta chemotherapy, ọgwụgwọ radieshon, ọgwụgwọ antiangiogenic, na ihe mgbochi ndị ọzọ na-enyocha ihe mgbochi dị ka CTLA-4, LAG-3, na TIGIT, ndị nchọpụta na-atụ anya ịkwalite nrụpụta nke immunotherapy ọzọ.

Enweghi nkwubi okwu na usoro kacha mma nke immunotherapy maka NSCLC n'oge a na-arụ ọrụ, karịsịa ma ọ bụrụ na ọ bụrụ na e jiri ya tụnyere neoadjuvant immunotherapy naanị, yana ma ihe mgbakwunye adjuvant immunotherapy nwere ike iweta mmetụta ndị ọzọ dị ịrịba ama, a ka nwere enweghị nsonaazụ nnwale.
Forde et al. jiri nyocha nyocha nke nyocha dị arọ iji mee ka mmetụta nke nnwale ndị a na-achịkwaghị achịkwa, wee gbanwee usoro ọnụọgụgụ ntọala na njirimara ọrịa n'etiti ọnụ ọgụgụ dị iche iche nke ọmụmụ iji belata mmetụta mgbagwoju anya nke ihe ndị a, na-eme ka nsonaazụ CheckMate 816 [1] na CheckMate 77T [8] tụnyere. Oge nleba anya nke etiti bụ ọnwa 29.5 (CheckMate 816) na ọnwa 33.3 (CheckMate 77T), n'otu n'otu, na-enye oge nleba anya zuru oke iji hụ EFS na usoro nrụpụta isi ndị ọzọ.
Na nyocha dị arọ, HR nke EFS bụ 0.61 (95% CI, 0.39 ruo 0.97), na-atụ aro 39% obere ihe ize ndụ nke nlọghachi azụ ma ọ bụ ọnwụ na perioperative nabuliumab jikọtara chemotherapy otu (CheckMate 77T mode) ma e jiri ya tụnyere neoadjuvant nabuliumab jikọtara chemotetherapy (81ck). The perioperative nebuliyuzumab plus chemotherapy otu gosiri a obere uru na ndị ọrịa niile n'oge mmalite, na mmetụta na-apụtakarị na ndị ọrịa na-erughị 1% tumo PD-L1 okwu (49% mbelata n'ihe ize ndụ nke nlọghachite ma ọ bụ ọnwụ). Tụkwasị na nke ahụ, maka ndị ọrịa na-emezughị pCR, ndị na-arụ ọrụ naburiumab jikọtara chemotherapy otu gosipụtara uru dị ukwuu nke EFS (mbelata 35% n'ihe ize ndụ nke nlọghachi ma ọ bụ ọnwụ) karịa neoadjuvant nabuliumab jikọtara chemotherapy. Nsonaazụ ndị a na-egosi na ụdị immunotherapy perioperative bara uru karịa ụdị immunotherapy neoadjuvant naanị, karịsịa na ndị ọrịa nwere obere okwu PD-L1 na ihe fọdụrụ na tumor mgbe ọgwụgwọ mbụ gasịrị.
Otú ọ dị, ụfọdụ ntụnyere na-apụtaghị ìhè (dị ka meta-analyses) egosila ọnweghị nnukwu ọdịiche dị na nlanarị n'etiti neoadjuvant immunotherapy na perioperative immunotherapy [18]. Nnyocha meta nke dabere na data onye ọrịa n'otu n'otu chọpụtara na immunotherapy perioperative na neoadjuvant immunotherapy nwere nsonaazụ yiri ya na EFS na ma pCR na ndị na-abụghị PCR na ndị ọrịa nwere NSCLC n'oge na-arụ ọrụ [19]. Tụkwasị na nke ahụ, onyinye nke usoro ọgwụgwọ adjuvant immunotherapy, karịsịa mgbe ndị ọrịa nwetasịrị pCR, na-anọgide na-ese okwu na ụlọ ọgwụ.
Na nso nso a, US Food and Drug Administration (FDA) Oncology Advisory Drugs Committee tụlere okwu a, na-ekwusi ike na ọrụ nke adjuvant immunotherapy ka amabeghị [20]. A tụlere ya na: (1) Ọ na-esiri ike ịmata mmetụta nke usoro ọgwụgwọ ọ bụla: n'ihi na mmemme perioperative nwere akụkụ abụọ, neoadjuvant na adjuvant, ọ na-esiri ike ikpebi onyinye nke onye ọ bụla nke usoro ọ bụla na mmetụta zuru oke, na-eme ka o sie ike ikpebi nke oge dị mkpa karị, ma ọ bụ ma ọ dị mkpa ka a rụọ usoro abụọ ahụ n'otu oge; (2) Ohere nke ọgwụgwọ gabigara ókè: ọ bụrụ na immunotherapy na-etinye aka na usoro ọgwụgwọ abụọ ahụ, ọ nwere ike ime ka ndị ọrịa nweta ọgwụgwọ ma mee ka ohere nke mmetụta ndị ọzọ dịkwuo elu; (3) Ịbawanye ibu ọgwụgwọ: ọgwụgwọ ọzọ na usoro ọgwụgwọ adjuvant nwere ike iduga n'ịgwọ ọrịa dị elu maka ndị ọrịa, karịsịa ma ọ bụrụ na ejighị n'aka banyere ntinye aka ya na njedebe zuru oke. Na nzaghachi na arụmụka a dị n'elu, iji nweta nkwubi okwu doro anya, ọ dị mkpa ka a na-enyocha ule a na-achịkwa nke ọma maka nyocha ọzọ n'ọdịnihu.