Immunotherapy na huhu na huhu, huhu ciwon daji immunotherapy, huhu ciwon daji PD-1 magani, da kuma huhu ciwon daji PD-L1 magani ne duk kana so ka sani.
In the past two years, immune checkpoint inhibitors have undoubtedly been one of the most successful tumor immunotherapies, which has changed the treatment prospects for NSCLC. The four PD-1 / L1 currently approved for lung cancer have improved the five-year survival rate of advanced lung cancer from less than 5% to 16%, which has tripled, and many patients and even doctors are excited. Immunotherapy is gradually becoming a “special effect” drug for the treatment of advanced cututtukan daji na kansa marasa kansar. Most kwayar cutar huhu patients still have many questions about PD-1 treatment, and today we will answer them one by one.
Menene PD-1 / L1 maganin ciwon huhu na huhu?
Immunotherapy is a therapy that uses the patient’s immune system to fight cancer. PD-1 / L1 treatment is called immune checkpoint inhibitor therapy and is a type of immunotherapy.
Maganin hanawa na rigakafi yana nufin: PD-1 furotin ne a saman ƙwayoyin T wanda ke taimakawa wajen sarrafa martanin garkuwar jiki. Lokacin da PD-1 ya ɗaure zuwa wani furotin da ake kira PDL-1 akan ƙwayoyin cutar kansa, yana hana ƙwayoyin T (kwayoyin rigakafi) daga kashe ƙwayoyin cutar kansa. Mai hanawa na PD-1 yana ɗaure zuwa PDL-1, don haka yana sakin garkuwar rigakafi na ƙwayoyin T da kuma dawo da ikon kashe ƙwayoyin kansa.
Menene PD-1 / L1 na yanzu wanda FDA ta amince da shi don maganin cutar huhu?
FDA ta amince da masu hana shinge na rigakafi guda huɗu: Nivolumab (O magani), pembrolizumab (K magani), atezolizumab (T magani) da durvalumab (I magani) don maganin ciwon huhu mara ƙarami.
| Sunan Magunguna | Pembrolizumab | Nivolumab | Attuzumab | Devaruzumab |
| Sunan Turanci | keytruda | Abin al'ajabi | Tecentriq | Imfinzi |
| manufacturer | Merck | Bristol-Myers | Roche | AstraZeneca |
| sashi | 2mg / kg sau ɗaya a kowane mako uku | 3mg / kg sau ɗaya a kowane mako biyu | 1200mg sau ɗaya kowane mako uku | 10mg / kg sau ɗaya a kowane mako biyu |
| Jerin | Jerin Amurka | Aka jera a Sin | Jerin Amurka | An jera su a China |
Menene alamomi ga kowane yarda da cutar kansa huhu PD-1 / L1?
Pabolizumab (Pembrolizumab, Pambrolizumab, Pembrolizumab) | Kerui Da (Jinheide, Keytruda) | K magani
| Alamar da aka amince (ciwon huhu) | Ko don gano PD-L1 |
| 1. Haɗe tare da pemetrexed da cisplatin / carboplatin don jiyya ta farko na marasa lafiya, masu ci gaba / koma baya marasa kanjamau marasa kansar huhu (NSCLC), ba tare da la’akari da bayanin PD-L1 ba. | babu |
| 2. An haɗa shi da carboplatin da paclitaxel / nab-paclitaxel (Abraxane) ga marasa lafiya da ciwon huhu na ciwon huhu da ƙananan ƙwayoyin cuta (NSCLC) waɗanda ba za a iya samun su ta hanyar jiyya ta farko ba, ba tare da la’akari da bayanin PD-L1 ba. | babu |
| 3. Single-agent, first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC), whose metastatic non-small cell lung cancer (NSCLC) tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%], by FDA approved test confirms that there are no EGFR or ALK genome tumo ɓarna | Ee, PD-L1≥50% |
| 4. Magungunan miyagun ƙwayoyi guda ɗaya ga marasa lafiya tare da ciwon huhu marasa ƙananan ƙwayoyin cuta (NSCLC), wanda ciwon daji ya bayyana PD-L1 ((TPS) ≥ 1%), ƙaddarar da FDA ta amince da gwaje-gwajen, ci gaba da cututtuka bayan ilimin chemotherapy na platinum. | Ee, PD-L1 ≥ 1% |
Nivolumab (Navumab, Niluumab, Nivolumab) | Odivo (Odivo, Odvo, Opdivo) | Ya miyagun ƙwayoyi
| Alamar da aka amince (ciwon huhu) |
| 1. Domin maganin ciwon huhu na huhu (metastatic) wanda ba ƙaramin ciwon sankarar huhu ba wanda har yanzu yana shan maganin platinum chemotherapy |
| 2. Domin jinyar marasa lafiya da ciwon huhu (ƙananan ƙwayar cuta) ƙwayar ƙwayar huhu (NSCLC) mai dacewa, wanda ya dace da marasa lafiya waɗanda ke da maganin cutar sankara na platinum ko waɗanda cutar ta lalace bayan chemotherapy |
Devarizumab (Duvaluzumab, Duvalizumab, Deluzumab, Durvalumab) | Magunguna (Imfinzi)
| Alamar da aka amince (ciwon huhu) |
| Ana amfani da shi don kula da ciwon huhu na cikin gida wanda ba ƙaramin ƙwayar huhu ba (NSCLC) wanda bai taɓa yin tiyata ba bayan an yi amfani da madaidaicin radiochemotherapy na tushen platinum. |
Attuzumab (Atezolizumab, Atezolizumab) | Maganin T (Tecentriq)
| Alamar da aka amince (ciwon huhu) |
| 1. Metastatic non-small cell cancer cancer wanda yanayinsa ke tabarbarewa a lokacin ko bayan chemotherapy dauke da platinum. Idan kansar mara lafiya ta ƙananan ƙwayar huhu ta canza a cikin ƙwayoyin EGFR ko ALK, yakamata a fara amfani da ƙwayoyin da ke yin niyya ga EGFR ko ALK canje-canje. |
| 2. An haɗa shi tare da chemotherapy (Abraxane [paclitaxel protein conjugate; nab-paclitaxel] da carboplatin) azaman magani na farko ga marasa lafiya da ƙananan ƙwayoyin cuta marasa kansar huhu (NSCLC) ba tare da EGFR ko ALK ba |
Yadda za a zaɓi PD-1 / L1 ga marasa lafiya da ciwon huhu na huhu
Yadda za a zaɓi huɗu masu hana shinge na bincike na ɗaya daga cikin matsalolin da ke damun masu cutar kansar huhu. Teburin da ke gaba suna taƙaita zaɓin shirin magani ga kowa da kowa dalla -dalla kuma a sarari.
Ciwon kansar huhu ba ƙananan ƙwayoyin cuta ba
Immunotherapy na farko don ciwon daji na huhu
| An saka | Shawarar matakin farko | Shawarar matakin 3 |
| PD-L1≥50% | Pembrolizumab monotherapy | |
| 1% ≤PD-L1≤49% | Squamous cell carcinoma: Pabolizumab
Carcinoma cell-squamous cell: Pabolizumab guda magani ko Pabolizumab haɗe da platinum + pemetrexed |
|
| PD-L1 ＜ 1% ko ba a sani ba | Ciwon kansar da ba ta motsa jiki ba: paclizumab hade da platinum + pemetrexed | Non-squamous cell carcinoma: atezumab combined with bevacizumab combined with chemotherapy (carboplatin and paclitaxel) |
Immunotherapy na layi na biyu don ciwon daji na huhu
| An saka | Shawarar matakin farko | Shawarar matakin 3 |
| Babu maganin PD-1 / L1 na baya | PD-L1 ba a sani ba ko kuma ba tare da la'akari da matsayin magana ba: nivolumab monotherapy | PD-L1 ba a sani ba ko kuma ba tare da la'akari da matsayin magana ba: atezumab monotherapy |
| Maganin PD-1 / L1 na baya | Magani mai hana PD-1 / L1 na baya: abun ciki na platinum yakamata a haɗa shi tare da chemotherapy (zaɓi chemotherapy da ya dace gwargwadon nau'in histological)
PD-1 / L1 maganin hana haihuwa wanda ya haɗu tare da chemotherapy: docetaxel ko wasu chemotherapy-wakili guda ɗaya (magungunan farko da ba a karɓa ba) |
Likitan rigakafi na uku don ciwon huhu na huhu: shawarwarin sakandare, nivolumab.
Marasa lafiya mataki uku marasa kanana ciwon huhu: Shawarar Grade III, karbar ƙarfafawa far tare da dufaliolizumab bayan radiotherapy da chemotherapy.
Ƙananan cel
l ciwon huhu na huhu tare da maye gurbi
Don rigakafin rigakafi na NSCLC tare da ingantaccen EFGR / ALK, har yanzu akwai isasshen shaida. IMPower150 sakamakon binciken ƙungiya -ƙungiya ya nuna cewa makirci mai zuwa yana da wani tasiri: atelizumab + bevacizumab + carboplatin + taxol
Wadanne alamomi ake buƙatar gwadawa kafin amfani da PD-1 / L1?
A halin yanzu, likitocin suna komawa ga bayyanar TMB da PD-L1 azaman alamomin rigakafin huhu da jiyya. Rossy ya tattara muku wata makala don fassara fassarorin halittu guda biyar waɗanda ke hasashen ingancin PD-1. Kuna iya nufin: Yadda za a yi hasashen ingancin PD-1 a gaba? Cikakken bincike na manyan masu hasashe biyar!
1) PD-L1
A halin yanzu, ana la'akari da cewa bayyanar PD-L1 a cikin kyallen kyallen takarda alama ce mafi dacewa don zaɓar yawan jama'a kafin maganin PD-1 / PD-L1. Amma a lokaci guda, akwai matsaloli da yawa a cikin gano PD-L1, kamar bambance-bambancen sararin samaniya, shin ƙaramin ɓangaren ɓarna na iya wakiltar duk jihar gaba ɗaya? Hakanan akwai rarrabuwa na ɗan lokaci, saboda bayan jiyya, PD-L1's Yanayin magana zai canza. Babu daidaituwa na gano immunohistochemical. Akwai ƙwayoyin rigakafi da yawa don PD-L1 immunohistochemical staining. Kyakkyawan ƙimar yarjejeniya ta ƙwayoyin rigakafi daban -daban shine kawai 73% -76%, wanda zai shafi sakamakon ganowa.
2) TMB
Binciken na yanzu yana nuna cewa TMB / bTMB azaman alamar tsinkaya don tasirin warkarwa na ICIs har yanzu yana da rigima.
Ga waɗancan marasa lafiya na cikin gida waɗanda kawai aka kamu da cutar sankarar huhu marasa ƙananan ƙwayar cuta, masana'antar kula da cutar kanjamau ta gida gaba ɗaya tana ba da shawarar gwajin PD-L1. Idan PD-L1 ≥ 50%, ko ƙwayar ƙwayar ƙwayar ƙwayar cuta ce ko ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta, sabon magani, maye gurbi wanda ba ƙaramin ƙwayar ƙwayar ƙwayar huhu ba za a iya kula da shi da magungunan K don samun babban damar samun fa'idar rayuwa a halin yanzu.
Tabbas, don aikace -aikacen asibiti na masu hana shinge na rigakafi, Amurka ita ce aka fi bincike kuma tana da ƙwarewar asibiti mafi wadata. Kwararrun masu cutar kansa na huhu a cikin Amurka sun dogara ne akan bayanan yanzu akan TMB da PD-L1 don chemotherapy da / ko immunotherapy na kansar huhu Marasa lafiya.
1. Anti-PD-1 monotherapy ana ba marasa lafiya da “zafi” ko kumburin kumburi tare da babban magana PD-L1 da TMB.
2. Ga marasa lafiya da yawan magana PD-L1 amma ƙarancin TMB, ba chemoimmunotherapy.
3. Ga waɗannan marasa lafiya waɗanda ke da babban TMB amma ƙarancin magana ko mara kyau PD-L1, ba chemoimmunotherapy ko anti-PD-1 / CTLA-4 far.
4. Bugu da ƙari, ga marasa lafiya masu ciwon “sanyi” ko marasa kumburi tare da ƙarancin TMB da ƙarancin PD-L1 magana, ana yin chemotherapy tare da ko ba tare da rigakafin rigakafi ko yuwuwar rigakafin ƙwayar cuta ba.
Rossy ya tunatar da yawancin masu cutar kansar huhu cewa kafin suyi amfani da PD-1, dole ne su zaɓi kamfani mai cikakken iko don gwajin biomarker, sannan kuma tuntuɓi Bei Shangguang ko ma sanannen masanin cutar huhu a Amurka don tsara madaidaicin shirin magani. , ko za su iya tuntuɓar masanin ilimin oncologist na duniya. Ma'aikatar Magungunan Yanar Gizo.
Shin marasa lafiya na PD-1 masu ƙarancin magana suna iya amfani da PD-1?
Ga waɗancan marasa lafiya waɗanda ke da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta wacce ba a taɓa gano ta ba, muddin maganganun PD-L1 tabbatacce ne, ko ƙwayar ƙwayar ƙwayar ƙwayar cuta ce ko ƙwayar ƙwayar ƙwayar ƙwayar cuta, yana iya yuwu a sami fa'idodin rayuwa daga farkon jiyya na K-monotherapy monotherapy, don haka ya tsawaita rayuwa. Wasu masana kuma suna ba da shawarar cewa marasa lafiya da ke da bayanin PD-L1 tsakanin 1-49% kuma suna iya amfani da K da chemotherapy idan za su iya jure wa jiyyar cutar sankara.
Za a iya amfani da PD-1 don sababbin marasa lafiya da ke da gwajin PD-L1 mara kyau?
Sakamakon kwanan nan da yawa na PD-1 monoclonal antibody hade da ilimin chemotherapy sun tabbatar da cewa koda gwajin PD-L1 ba ta da kyau, ko kuma ba a gwada PD-L1 da sharaɗi ba, PD-1 monoclonal antibody haɗe tare da chemotherapy na iya magance ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta wadda ta haɗa da nazarin ilimin chemotherapy. carcinoma na sel. Marasa lafiyar ciwon huhu na huhu suna kawo fa'idodin rayuwa mafi mahimmanci tare da ilimin cutar kansa kawai.
Ga marasa lafiya da ciwon huhu na huhu na PD-L1 mara kyau, ba tare da la’akari da ko suna da ciwon huhu na huhu ko na huhu ba, idan ba su sami chemotherapy ba kafin, bayan sun karɓi K hade chemotherapy, idan aka kwatanta da chemotherapy kadai Duk marasa lafiya na iya samun fa'idar rayuwa mafi tsayi. Irin waɗannan bayanan albishir ne ga waɗancan marasa lafiya waɗanda ke da mummunan magana PD-L1 ko babu yanayin gano PD-L1.
Shin marasa lafiya da ke shan maganin chemotherapy na iya canzawa ko ƙara PD-1?
Ko da kuwa ko yana da ƙanƙantar da kai ko kuma ba ƙaramin ciwon daji na huhu na huhu ba, tasirin K haɗe da chemotherapy tabbas ya fi chemotherapy kaɗai, amma marasa lafiya da ke karɓar maganin cutar sankara suna karɓar PD-1 monoclonal antibody? Menene mafi kyawun tasirin chemotherapy?
Bayan radiotherapy da chemotherapy, zai kashe wasu ƙwayoyin tumor, ta haka yana sakin antigens tumor da ƙarfafa garkuwar ɗan adam. A wannan lokacin, idan aka ba PD-1 monoclonal antibody treatment, a ka'ida, tasirin maganin kumburin zai yi ƙarfi. A halin yanzu, akwai sakamakon bincike na farko wanda ke nuna cewa maganin rigakafin rigakafi na PD-1 monoclonal antibody ko PD-L1 monoclonal antibody bayan lokaci guda radiotherapy da chemotherapy yana da tasiri mai kyau kuma yana ƙara tsawon rayuwa.
Marasa lafiya waɗanda aka gano su kawai yakamata su fara fara ilimin chemotherapy da farko, sannan zaɓi PD-1 ko amfani da PD-1 kai tsaye bayan juriya na miyagun ƙwayoyi
Ga waɗancan marasa lafiya da ke fama da ciwon daji na ƙananan ƙwayoyin cuta waɗanda ba a gano su ba, amfani da farkon PD-1 monoclonal antibody zai kawo fa'idodin rayuwa mafi kyau fiye da amfani da ƙarshen.
Me za a yi bayan juriya na PD-1?
Marasa lafiya tare da masu hana PD-1 masu tasiri gabaɗaya suna da sakamako na dindindin; duk da haka, kusan kashi 30% na marasa lafiya an lura suna da juriya na cuta. Maɓalli don shawo kan juriya na miyagun ƙwayoyi galibi maki biyu ne:
Na farko, idan ya yiwu, za a iya yin biopsy da zurfin bincike na rigakafi akan sabbin wuraren da aka ƙara ko ƙara yawan juriya na miyagun ƙwayoyi don nemo musabbabin jurewar miyagun ƙwayoyi da yin magani bisa ga sanadin. Misali, wasu marassa lafiya sun kasance saboda babban lada na TIM-3, LAG-3 ko IDO; sannan zaɓi, mai hana PD-1 haɗe tare da mai hana TIM-3, LAG-3 antibody, IDO inhibitor shine mafi kyawun maganin magani.
Abu na biyu, ga marasa lafiya waɗanda ba za su iya tantance sanadin tsayayyar miyagun ƙwayoyi ba, za su iya haɗa takamaiman yanayi don zaɓar abokin haɗin gwiwa mafi kyau don juyar da juriya na miyagun ƙwayoyi da tsawaita rayuwa; ko, canzawa zuwa jiyya na gargajiya kamar radiotherapy da chemotherapy, sa baki, mitar rediyo, da shigar da ƙwayoyin cuta.
A ƙarshe, kuma mafi mahimmanci, ƙarin ƙarin shaidu suna tallafawa cewa maganin rigakafi irin su masu hana PD-1 ya kamata a yi amfani da su da wuri-wuri lokacin da yanayin haƙuri ya fi kyau kuma nauyin tumo ba shi da yawa.
