I-immunotherapy yomdlavuza wamaphaphu, lung cancer immunotherapy, lung cancer PD-1 treatment, and lung cancer PD-L1 treatment are all you want to know.
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 umdlavuza wamaphaphu weselula ongewona omncane. Iningi umdlavuza wamaphaphu patients still have many questions about PD-1 treatment, and today we will answer them one by one.
Kuyini ukwelashwa kwe-PD-1 / L1 yomdlavuza wamaphaphu?
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.
Immune checkpoint inhibitor therapy refers to: PD-1 is a protein on the surface of T cells that helps control the body’s immune response. When PD-1 binds to another protein called PDL-1 on cancer cells, it prevents T cells (an immune cell) from killing cancer cells. The PD-1 inhibitor binds to PDL-1, thereby releasing the immune suppression of T cells and regaining the ability to kill cancer cells
Yini i-PD-1 / L1 yamanje evunyelwe yi-FDA ekwelashweni komdlavuza wamaphaphu?
The FDA approved four immune checkpoint inhibitors: Nivolumab (O drug), pembrolizumab (K drug), atezolizumab (T drug) and durvalumab (I drug) for the treatment of non-small cell lung cancer.
| Igama Lesidakamizwa | I-Pembrolizumab | UNivolumab | I-Attuzumab | UDevaruzumab |
| Igama lesiNgisi | Keytruda | I-Opdivo | I-Tecentriq | Imfinzi |
| nomakhi | Merck | IBristol-Myers | Roche | I-AstraZeneca |
| Isikali | 2mg / kg kanye njalo emavikini amathathu | 3mg / kg kanye njalo emavikini amabili | 1200mg kanye njalo emavikini amathathu | 10mg / kg kanye njalo emavikini amabili |
| Ukufakwa ohlwini | Uhlu lwase-US | Kubhalwe ku- China | Uhlu lwase-US | Kubhalwe eChina |
Yiziphi izinkomba zokuvunyelwa komdlavuza ngamunye wamaphaphu PD-1 / L1?
I-Pabolizumab (Pembrolizumab, Pambrolizumab, Pembrolizumab) | I-Kerui Da (Jinheide, Keytruda) | K isidakamizwa
| Izinkomba ezivunyelwe (umdlavuza wamaphaphu) | Ukuthi ungathola i-PD-L1 |
| 1. Kuhlanganiswe ne-pemetrexed ne-cisplatin / carboplatin yokwelashwa kolayini wokuqala kweziguli zomdlavuza wamaphaphu ezinganqamuki, ezingaphakeme / ezibuyiselwe emuva ezingekho emincane, ngaphandle kokubhekiswa kwe-PD-L1 | cha |
| 2. Kuhlanganiswe ne-carboplatin ne-paclitaxel / nab-paclitaxel (i-Abraxane) yeziguli ezinomdlavuza wamaphaphu wesifo samangqamuzana asezingeni eliphakeme / eliphindaphindayo (NSCLC) ezingatholakali ngokwelashwa komugqa wokuqala, ngaphandle kokubhekiswa kwe-PD-L1 | cha |
| 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 isisu aberrations | Yebo, PD-L1≥50% |
| 4. Single drug treatment for patients with metastatic non-small cell lung cancer (NSCLC), whose tumor expresses PD-L1 ((TPS) ≥ 1%), determined by FDA approved trials, disease progression after platinum-based chemotherapy | Yebo, PD-L1 ≥ 1% |
INivolumab (Navumab, Niluumab, Nivolumab) | I-Odivo (Odivo, Odvo, Opdivo) | O isidakamizwa
| Izinkomba ezivunyelwe (umdlavuza wamaphaphu) |
| 1. Ukwelashwa komdlavuza wamaphaphu weseli ongaphakeme (we-metastatic) ongeyona encane osalungiswa ngamakhemikhali e-platinum |
| 2. Ukwelashwa kweziguli ezinomdlavuza wamaphaphu wesifo samangqamuzana asithuthukile (metastatic) squamous non-small (NSCLC), ezilungele iziguli ezine-plotherapy-based chemotherapy noma isifo sayo esonakele ngemuva kwe-chemotherapy |
UDevarizumab (iDuvaluzumab, iDuvalizumab, iDeluzumab, iDurvalumab) | I drug (Imfinzi)
| Izinkomba ezivunyelwe (umdlavuza wamaphaphu) |
| Isetshenziselwa ukwelapha umdlavuza wamaphaphu wesifo samangqamuzana ongaphakeme (NSCLC) ongakatholakali ekuhlinzekweni kokuhlinzwa ngemuva kokwenza i-radiochemotherapy esezingeni elijwayelekile eseplatinamu |
I-Attuzumab (Atezolizumab, Atezolizumab) | Isidakamizwa i-T (Tecentriq)
| Izinkomba ezivunyelwe (umdlavuza wamaphaphu) |
| 1. Umdlavuza wamaphaphu weseli ongesona omncane wesimo saso esiwohloka ngesikhathi nangemva kwe-chemotherapy equkethe i-platinum. Uma umdlavuza wamaphaphu wesiguli ongewona omncane uguquka kuzakhi zofuzo ze-EGFR noma ze-ALK, izidakamizwa eziqondiswe kumangqamuzana ezibhekise ku-EGFR noma izinguquko zofuzo ze-ALK kufanele zisetshenziswe kuqala, njll. |
| 2. Kuhlanganiswe nokwelashwa ngamakhemikhali (i-Abraxane [paclitaxel protein conjugate; nab-paclitaxel] ne-carboplatin) njengokwelashwa komugqa wokuqala kweziguli ezinomdlavuza wamaphaphu wesifo samangqamuzana ongewona omncane (NSCLC) ngaphandle kwe-EGFR noma i-ALK |
Ungayikhetha kanjani iPD-1 / L1 yeziguli ezinomdlavuza wamaphaphu
Ungawakhetha kanjani ama-inhibitors amane okuhlola izivikeli mzimba angenye yezinkinga ezithinteka kakhulu zeziguli ezinomdlavuza wamaphaphu. Amatafula alandelayo afingqa ukukhetha kohlelo lokwelashwa kwawo wonke umuntu ngokuningiliziwe nangokucacile.
Umdlavuza wamaphaphu weseli ongelona elincane
I-immunotherapy yomugqa wokuqala yomdlavuza wamaphaphu osezingeni eliphakeme
| Kukhethiwe | Ukuncoma kwezinga lokuqala | Izinga le-3 |
| I-PD-L1≥50% | I-Pembrolizumab monotherapy | |
| 1% ≤PD-L1≤49% | I-squamous cell carcinoma: iPabolizumab
I-non-squamous cell carcinoma: Isidakamizwa esisodwa sePabolizumab noma iPabolizumab kuhlanganiswe neplatinum + pemetrexed |
|
| PD-L1 ＜ 1% noma akwaziwa | I-non-squamous cell carcinoma: i-paclizumab ihlanganiswe ne-platinum + pemetrexed | Non-squamous cell carcinoma: atezumab combined with bevacizumab combined with chemotherapy (carboplatin and paclitaxel) |
I-immunotherapy yomugqa wesibili womdlavuza ophuthumayo wamaphaphu
| Kukhethiwe | Ukuncoma kwezinga lokuqala | Izinga le-3 |
| Akukho ukwelashwa okwedlule kwe-PD-1 / L1 | I-PD-L1 ayaziwa noma kungakhathalekile isimo sesisho: nivolumab monotherapy | I-PD-L1 ayaziwa noma kungakhathalekile isimo sesisho: atezumab monotherapy |
| Ukwelashwa kwangaphambilini kwe-PD-1 / L1 | Ukwelashwa okwedlule kwe-PD-1 / L1 inhibitor: okuqukethwe kwe-platinum kufanele kuhlanganiswe ne-chemotherapy (khetha i-chemotherapy efanelekile ngohlobo lwe-histological)
Ukwelashwa okwedlule kwe-PD-1 / L1 inhibitor kuhlanganiswe ne-chemotherapy: i-docetaxel noma enye i-chemotherapy ye-single-agent (umugqa wokuqala wezidakamizwa ezingatholakali) |
I-immunotherapy yomugqa wesithathu yomdlavuza wamaphaphu osezingeni eliphakeme: izincomo zesibili, i-nivolumab.
Three-stage unresectable non-small cell lung cancer: Grade III recommendation, receiving consolidation therapy with dufaliolizumab after radiotherapy and chemotherapy.
Iseli elincane
l umdlavuza wamaphaphu ngokuguquka komzimba
Okwe-immunotherapy kwe-NSCLC ene-EFGR / ALK enhle, kusenobufakazi obanele. IMpower150 imiphumela yokuhlaziywa kweqembu elincane ibonisa ukuthi uhlelo olulandelayo lunomphumela othile: atelizumab + bevacizumab + carboplatin + taxol
Yiziphi izinkomba ezidinga ukuhlolwa ngaphambi kokusebenzisa i-PD-1 / L1?
Njengamanje, odokotela babhekisa ekuvezweni kwe-TMB ne-PD-L1 njengezimpawu ze-lung immunotherapy kanye ne-chemotherapy. URossy uhlanganise i-athikili ukuze uhumushe ama-biomarker amahlanu abikezela ukusebenza kwe-PD-1. Ungabheka ku: Ungakubikezela kanjani ukusebenza kwe-PD-1 kusengaphambili? Ukuhlaziywa okuphelele kwababikezeli abahlanu abakhulu!
1) PD-L1
Njengamanje, kubhekwa ukuthi ukubonakaliswa kwe-PD-L1 ezicutshini zesimila kuyimpawu efanelekile yokukhetha inani labantu eliphakeme ngaphambi kokwelashwa kwe-anti-PD-1 / PD-L1. Kepha ngasikhathi sinye, kunezinkinga eziningi ekutholakaleni kwe-PD-L1, okufana ne-spatial heterogeneity, ingabe ingxenye encane yesimila ingamela sonke isimo sesimila sonke? Kukhona ne-heterogeneity yesikhashana, ngoba ngemuva kokwelashwa, i-PD-L1's Isimo sesisho sizoshintsha. Akukho ukulinganiswa kokutholwa kwe-immunohistochemical. Kunama-antibodies amaningi we-PD-L1 immunohistochemical staining. Izinga lesivumelwano esivumayo sama-antibodies ahlukene angama-73% -76% kuphela, okuzothinta imiphumela yokutholwa.
2) TMB
Ucwaningo lwamanje lubonisa ukuthi i-TMB / bTMB njengophawu lokuqagela lomphumela wokwelashwa kwama-ICIs isengumbango.
Kulezo ziguli ezifuywayo ezisanda kutholakala zinomdlavuza ongaphakeme weselula wamaphaphu, imboni yokwelashwa komdlavuza wasemaphandleni ngokuvamile incoma ukuhlolwa kwe-PD-L1. Uma i-PD-L1 ≥ 50%, noma ngabe i-squamous cell carcinoma noma i-non-squamous cell carcinoma, iziguli ezisanda kwelashwa, ezingezona zofuzo ezingezona ezincane zomdlavuza wamaphaphu zingaphathwa ngemithi ka-K ukuthola ithuba elikhulu lokusinda okwamanje.
Vele, ekusetshenzisweni komtholampilo kwama-immune checkpoint inhibitors, i-United States iyona ecwaningwe kakhulu futhi inesipiliyoni somtholampilo esicebe kakhulu. Ochwepheshe abanegunya lomdlavuza wamaphaphu e-United States basuselwa kulwazi lwamanje ku-TMB naku-PD-L1 lwe-chemotherapy kanye / noma i-immunotherapy yomdlavuza wamaphaphu Iziguli ziboshwe.
1. I-anti-PD-1 monotherapy inikezwa iziguli ezinezicubu "ezishisayo" noma ezivuvukele ezinenkulumo ephezulu ye-PD-L1 ne-TMB.
2. Ezigulini ezinenkulumo ephezulu ye-PD-L1 kodwa ene-TMB ephansi, nikeza i-chemoimmunotherapy.
3. Kulezo ziguli ezine-TMB ephezulu kepha isisho esiphansi noma esibi se-PD-L1, nikeza i-chemoimmunotherapy noma i-anti-PD-1 / CTLA-4 therapy.
4. Ngaphezu kwalokho, ezigulini ezinezicubu “ezibandayo” noma ezingezona ukuvuvukala ezine-TMB ephansi nesisho esiphansi noma esibi se-PD-L1, i-chemotherapy yenziwa nge-immunotherapy noma ngaphandle kwayo noma i-immunotherapy yeselula.
URossy ukhumbuza iningi leziguli ezinomdlavuza wamaphaphu ukuthi ngaphambi kokusebenzisa iPD-1, kufanele zikhethe inkampani egunyazayo yokuhlola ukuhlolwa kwe-biomarker, bese ibonisana noBean Shangguang noma isazi somdlavuza wamaphaphu esaziwayo e-United States ukwakha uhlelo olucacile lwemithi , noma bangaxhumana nodokotela womdlavuza womhlaba wonke. UMnyango Wezokwelapha.
Ngabe iziguli ze-PD-1 ezinesisho esiphansi zingasebenzisa i-PD-1?
Kulezo ziguli ezine-cell non-small advanced advanced ezisanda kutholakala, inqobo nje uma i-PD-L1 expression is positive, noma ngabe i-squamous cell carcinoma noma i-non-squamous cell carcinoma, kungenzeka ukuthola izinzuzo zokusinda kusuka ekuqaleni ukwelashwa kwe-K-drug monotherapy, ngaleyo ndlela kwandise impilo. Abanye ochwepheshe baphinde basikisela ukuthi iziguli ezine-PD-L1 expression ephakathi kuka-1-49% nazo zingasebenzisa i-K plus chemotherapy uma zingakwazi ukubekezelela ukwelashwa ngamakhemikhali.
Ngabe i-PD-1 ingasetshenziselwa iziguli ezisanda kuphathwa ezinokuhlolwa okungalungile kwe-PD-L1?
Imiphumela yakamuva ye-PD-1 monoclonal antibody ehlanganisiwe yocwaningo lwe-chemotherapy ifakazile ukuthi noma ngabe ukuhlolwa kwe-PD-L1 kungalungile, noma i-PD-L1 ingavivinywa ngemibandela, i-PD-1 monoclonal antibody ehlanganiswe ne-chemotherapy ingelapha i-squamous cell carcinoma noma i-non-squamous i-carcinoma yeseli. Iziguli zomdlavuza wamaphaphu weselula ziletha izinzuzo ezibaluleke kakhulu zokusinda ngamakhemikhali kuphela.
Iziguli ezine-PD-L1-negative non-small cell cancer cancer, kungakhathalekile ukuthi zinomdlavuza wesifo samangqamuzana ongeyena omncane noma ongeyena owesigaxa, uma zingazange zithole i-chemotherapy ngaphambili, ngemuva kokuthola i-K chemotherapy ehlangene, uma kuqhathaniswa ne-chemotherapy iyodwa Zonke iziguli zingathola inzuzo ende yokuphila. Idatha enjalo iyizindaba ezinhle zalezo ziguli ezine-expression ye-PD-L1 engemihle noma asikho isimo sokuthola iPD-L1.
Ngabe iziguli ezelashwa ngamakhemikhali zingashintsha noma zengeze iPD-1?
Kungakhathalekile ukuthi uwumdlavuza wesifo samangqamuzana ongewona omncane noma omuncu, umphumela we-K ohlanganiswe ne-chemotherapy ungcono impela kune-chemotherapy kuphela, kepha iziguli ezithola i-chemotherapy zingathola i-PD-1 monoclonal antibody? Uyini umphumela ongcono we-chemotherapy?
Ngemuva kwe-radiotherapy kanye ne-chemotherapy, izobulala amangqamuzana athile wesimila, ngaleyo ndlela ikhiphe ama-tumor antigens futhi ivuselele ukuzivikela komzimba kwabantu. Ngalesi sikhathi, uma kunikezwa ukwelashwa kwe-PD-1 monoclonal antibody, ngokweqiniso, umphumela wokulwa nesimila uzoqina. Njengamanje, kunemiphumela yokuqala yocwaningo ekhombisa ukuthi ukwelashwa kokulondolozwa komzimba kwe-PD-1 monoclonal antibody noma i-PD-L1 antibody monoclonal antibody ngemuva kwe-radiotherapy kanye ne-chemotherapy kanyekanye kunomphumela omuhle futhi kuyandisa kakhulu impilo.
Iziguli ezisanda kutholakala kufanele ziqale i-chemotherapy kuqala, bese zikhetha i-PD-1 noma zisebenzise i-PD-1 ngqo ngemuva kokumelana nemithi
Kulezo ziguli ezinomdlavuza weseli ongekho omncane othuthukile osanda kutholakala, ukusetshenziswa kokuqala kwe-PD-1 monoclonal antibody kuzoletha izinzuzo zokusinda ezingcono kunokusebenzisa sekwedlule isikhathi.
Yini okufanele uyenze ngemuva kokumelana ne-PD-1?
Iziguli ezine-PD-1 inhibitors eziphumelelayo ngokuvamile zinemiphumela ehlala isikhathi eside; kodwa-ke, cishe iziguli ezingama-30% ziye zabonwa ukuthi zinokumelana nezifo. Isihluthulelo sokunqoba ukungazweli emithini ikakhulukazi amaphuzu amabili:
Okokuqala, uma kungenzeka, ukuhlaziywa kwe-biopsy nokujula komzimba kungenziwa ezindaweni ezisanda kufakwa noma ezandayo zokumelana nemithi ukuthola imbangela yokungazweli kwezidakamizwa kanye nokwelashwa ngokuvumelana nesizathu. Isibonelo, ezinye iziguli kungenxa yokubuyiselwa okuphezulu kwe-TIM-3, LAG-3 noma i-IDO; bese ukhetha, i-PD-1 inhibitor ihlanganiswe ne-TIM-3 inhibitor, i-LAG-3 antibody, i-IDO inhibitor izixazululo ezingcono kakhulu zokwelashwa.
Okwesibili, ezigulini ezingakwazi ukuthola imbangela yokwenqaba kwemithi, zingahlanganisa izimo ezithile ukuze zikhethe umlingani ohlanganyele ongcono kunabo bonke ukubuyisela emuva ukungazweli kwezidakamizwa nokwandisa isikhathi sokuphila; noma, shintshela ekwelashweni kwendabuko njenge-radiotherapy ne-chemotherapy, ukungenelela, imvamisa yomsakazo, nokufakwa kwezinhlayiyana.
Okokugcina, futhi okubaluleke kakhulu, ubufakazi obuningi obandayo buyasekela ukuthi i-immunotherapy efana ne-PD-1 inhibitors kufanele isetshenziswe ngokushesha okukhulu lapho isimo sesiguli singcono futhi umthwalo wesimila mncane.
