Kev tshuaj xyuas cov kev kho mob rau Advanced Renal Cell Carcinoma: Puas Tseem Muaj Qhov Chaw Rau Tyrosine Kinase Inhibitor (TKI) Monotherapy
Jul 10, 2023
TSAB NTAWV
Lub raum cell carcinoma (RCC) muaj ib pab pawg neeg heterogeneous ntawm lub raum qog ua raws li cov caj ces- thiab epigenetic-driven mechanisms thiab molecular pathways. Yog li, kev teb rau kev kho mob yog qhov sib txawv ntawm cov neeg mob, ntxiv txheej txheej ntxiv rau cov txheej txheem kev txiav txim siab kho mob nyuaj. Xyoo kaum xyoo dhau los coj qhov kev hloov pauv tsis tau pom dua hauv kev kho mob mus rau qib siab lossis metastatic RCC; Qhov tseeb, kev siv tshuaj tiv thaiv kab mob sib xyaw ua ke tau hloov pauv cov neeg mob cov kev kho mob arsenal thiab cov txiaj ntsig kho mob. Cov thawj coj thoob ntiaj teb cov txheej txheem sai sai tau txais cov tswv yim no ua cov qauv tshiab ntawm kev saib xyuas. Txawm li cas los xij, qhov kev ua tau zoo dua no los ntawm kev siv nyiaj ntev, nrog rau kev kwv yees tsis zoo rau cov neeg mob lub neej zoo. Tsis tas li ntawd, pawg pab pawg thiab kev soj ntsuam tom qab hoc ntawm cov kev sim tshuaj loj tau pom tias tsis yog txhua tus neeg mob tau txais txiaj ntsig sib npaug los ntawm cov txheej txheem tshiab no. Hauv cov ntsiab lus no, ib pab pawg kws tshaj lij ntawm lub raum mob qog noj ntshav tau ntsib thiab sib tham txog lub xeev ntawm kev kos duab hauv kev ua haujlwm, nrog rau qhov tshwj xeeb ntawm qhov tsim nyog ntawm kev siv monotherapy nrog anti-angiogenesis tyrosine kinase inhibitor (TKI) los kho cov pab pawg ntawm cov neeg mob. nrog RCC. Tsab ntawv xov xwm no tshuaj xyuas cov ntsiab lus tseem ceeb uas tau txiav txim siab tias muaj feem cuam tshuam rau qhov kev sib tham thiab tsim cov profile ntawm cov neeg mob uas TKI monotherapy tseem yog qhov kev xaiv ua ntej los ntawm kev zam dhau kev kho mob thiab tsis tsim nyog raug rau kev kho mob toxicity.
Ntsiab lus
Advanced los yog metastatic raum cell carcinoma (mRCC); Immune checkpoint inhibitor (ICI); Monotherapy; Tyrosine kinase inhibitor (TKI).
Nyem qhov no kom paub tias Cistanche yog dab tsi
Taw qhia
Lub raum cell carcinoma (RCC) yog ib pawg ntawm cov kab mob sib txawv uas suav nrog 2 feem pua ntawm kev kuaj mob qog noj ntshav thoob ntiaj teb thiab kev tuag [1]. Koom nrog ntau yam kev pheej hmoo uas yog tus yam ntxwv ntawm lub ntiaj teb niaj hnub no, RCC qhov xwm txheej tau nce zuj zus hauv lub ntiaj teb tsim, tam sim no yog qhov thib xya feem ntau neoplasm hauv cov cheeb tsam no [1, 2]. Nco ntsoov, RCC muaj cov neeg tuag ntau tshaj plaws ntawm urological neoplasms; whereastheoverall5-xyoosurvivalrateis76 feem pua , tus nqi no poob qis mus rau 12 feem pua ntawm cov neeg mob uas muaj kab mob theem IV [1]. Tsis tas li ntawd, kwv yees li 30 feem pua ntawm cov neeg mob tshiab tau kuaj mob RCC muaj tus kab mob metastatic, thaum 20-50 feem pua ntawm cov neeg mob kho mob hauv zos yuav rov qab los thiab nce mus rau theem metastatic [1, 3]. Qhov tseem ceeb, lwm txoj kev kho mob tseem tsis tau pom zoo rau qhov chaw nyob hauv Europe.
RCC qhov xwm txheej thiab cov neeg tuag tau sib txawv raws li nws cov subtype; Qhov tseeb, RCC suav nrog ib pawg ntawm cov koom haum ywj pheej histological, uas yog tus cwj pwm los ntawm kev hloov pauv caj ces thiab epigenetic thiab txoj hauv kev molecular, thiab yog li ntawd, lawv teb rau kev kho mob [4, 5]. Qhov feem ntau RCC subtype yog cov cell ntshiab, uas suav txog 70-75 feem pua ntawm tag nrho cov mob. Los ntawm ib qho kev xav ntawm caj ces, hom kab mob no yog tus cwj pwm los ntawm kev poob ntawm caj npab luv luv ntawm chromosome 3, uas encodes cov qog nqaij hlav gene VHL (von Hippel-Lindau) [4, 6, 7]. Lwm cov ntaub ntawv RCC feem ntau yog pawg nyob rau hauv lub kaus mom: cov subtypes tsis meej. Ntawm cov no, cov papillary variant muaj qhov tshwm sim ntau tshaj plaws, suav nrog 15 feem pua ntawm tag nrho cov qog nqaij hlav hauv lub raum [4, 6, 8]. Chromophobe RCC, uas tshwm sim nyob rau hauv 5-10 feem pua ntawm tag nrho cov mob, muaj ib tug feem ntau indolent chav kawm, txawm hais tias nws yog ib qho nyuaj rau kho ib zaug nws tau metastasized [4, 6, 7]. Sau cov kab mob qog nqaij hlav thiab lub raum medullary carcinoma account rau tsawg dua 5 feem pua ntawm tag nrho cov mob RCC. Cov subtypes tsis tshua muaj feem ntau yog txhoj puab heev, feem ntau tiv taus rau feem ntau txoj kev kho mob uas muaj rau hnub tim [6, 7]. Thaum kawg, kwv yees li 5 feem pua ntawm tag nrho cov mob RCC muaj cov yam ntxwv sarcomatoid; sarcomatoid RCC feem ntau yog cov tsos mob thiab ua rau muaj kev txhoj puab heev, thiab nws cov txiaj ntsig zoo yuav phem dua li cov mob uas tsis yog sarcomatoid [9, 10].
Txawm hais tias ntawm cov cell subtype meej, qib siab lossis metastatic RCC (mRCC) paub tias muaj ntau yam tsis zoo nyob rau hauv cov nqe lus ntawm kev kho mob thiab kev kho mob. Vim li ntawd, ob peb tus qauv kev pheej hmoo raug tsim tawm, uas ob feem ntau siv yog Memorial Sloan Kettering Cancer Center qauv (MSKCC) thiab International mRCC Database Consortium qauv (IMDC). Tus qauv MSKCC tau ua raws li kev txheeb xyuas rov qab ntawm 463 cov neeg mob nrog mRCC kho nrog interferon-a, uas cov kws sau ntawv tuaj yeem txheeb xyuas tsib yam kev pheej hmoo: Karnofsky kev ua haujlwm qis (tsawg dua 80 feem pua), ntshav siab lactate dehydrogenase (siab dua 1.5). lub sij hawm ntawm kev txwv sab sauv ntawm ib txwm muaj), qis hemoglobin (qis qis qis ntawm qhov qub), kho cov tshuaj calcium ntau hauv cov ntshav (siab dua 10 mg / dL) thiab lub sijhawm luv luv ntawm kev kuaj mob thawj zaug thiab kev kho mob pib (tsawg dua 1 xyoos) [11] ]. Cov neeg mob tau muab faib ua peb pawg raws li tus naj npawb ntawm cov kev pheej hmoo tam sim no: cov uas tsis muaj kev pheej hmoo raug cais raws li qhov txaus ntshai; cov uas muaj ib los yog ob qho kev pheej hmoo raug cais raws li qhov kev pheej hmoo nruab nrab; thiab cov uas muaj peb lossis ntau qhov kev pheej hmoo raug muab cais ua qhov pheej hmoo tsis zoo. Raws li, qhov nruab nrab tag nrho cov ciaj sia taus (OS) yog 30, 14, thiab 5 lub hlis nyob rau hauv txhua pab pawg, raws li [11]. IMDC tau tsim tawm ob peb xyoos tom qab, ua raws li kev txheeb xyuas rov qab ntawm 645 cov neeg mob nrog mRCC kho nrog qog vasculature-targeted therapy. Cov kws sau ntawv IMDC khaws plaub MSKCC qhov kev pheej hmoo - qis Karnofsky kev ua tau zoo (tsawg dua 80 feem pua), cov tshuaj kho cov tshuaj calcium ntau (tso siab tshaj qhov txwv ntawm ib txwm), qis hemoglobin (qis qis dua li qub), thiab lub sijhawm luv luv ntawm qhov pib. Kev kuaj mob thiab kev kho mob pib (tsawg dua 1 xyoos) - thiab ntxiv cov neutrophil thiab platelet suav (tso siab tshaj qhov txwv ntawm ib txwm muaj) [12]. Tom qab 2 xyoos, 75 feem pua ntawm cov neeg mob uas muaj kev pheej hmoo tseem muaj sia nyob, xws li 53 feem pua ntawm cov neeg mob uas muaj kev pheej hmoo nruab nrab thiab 7 feem pua ntawm cov neeg mob tsis zoo [12]. Tom qab ntawd, ntau qhov kev hloov kho tau ua rau cov qauv no, los ua pov thawj lawv hauv qhov chaw khaws cia [13, 14] lossis suav nrog lwm yam tseem ceeb, xws li qhov chaw metastasis [15]. Txawm li cas los xij, txawm hais tias muaj ntau qhov kev lees paub, cov qauv qub ntawm cov qauv kev kuaj mob no tseem siv tau ob qho tib si hauv kev sim tshuaj thiab thaum lub sijhawm ua haujlwm kho mob niaj hnub.
Kev tswj hwm qib siab lossis mRCC tau hloov pauv ntau dhau 30 xyoo dhau los. Thaum pib raws li kev tiv thaiv kab mob tsis tshwj xeeb (high-dose interleukin-2 [IL-2] thiab interferon-a), cov tswv yim no tau hloov zuj zus mus rau lub hom phiaj ntawm cov qog vasculature, intracellular oncogenic pathways, thiab lub cev tiv thaiv kab mob. signaling cascade. Cov neeg ua haujlwm tshiab tau ntxiv rau mRCC therapeutic armamentarium suav nrog vascular endothelial growth factor (VEGF)-targeted molecules, inhibitors ntawm lub hom phiaj ntawm rapamycin (mTOR), thiab cov tshuaj tiv thaiv kab mob tshiab (ICIs) [3, 6]. Tsis ntev los no, cov txheej txheem thoob ntiaj teb tau qhia txog kev sib koom ua ke ntawm ob tus neeg sawv cev no (ICI / ICI lossis ICI / VEGF-targeted agent) uas yog lub tswv yim zoo tshaj plaws los tswj cov cell ntshiab mRCC [16–18]. Txawm li cas los xij, txawm tias qhov txiaj ntsig tsis txaus ntseeg ntawm cov tswv yim sib xyaw ua ke - uas tau pom nyob rau hauv ntau qhov kev sim tshuaj - lawv kuj sawv cev rau kev txhim kho toxicity thaum piv nrog monotherapy, nrog rau kev kwv yees tsis zoo rau tus neeg mob lub neej zoo (QoL), thiab tej zaum yuav txwv qhov kev xaiv tom ntej. kho kab. Txawm hais tias qhov no tuaj yeem yog los ntawm cov tshuaj tiv thaiv VEGF tyrosine kinase inhibitor (TKI) siv (xws li pazopanib lossis sunitinib), qhov ua tau zoo ntawm cov tshuaj toxicity hauv qhov chaw metastatic yuav tsum tau ua tib zoo saib xyuas. Txawm li cas los xij, txawm tias kev kho mob sib xyaw ua ke yog ib qho kev xaiv zoo tshaj plaws los kho mRCC yog cov lus nug tseem tsis tau teb. Txawm hais tias qhov ua tau zoo ntawm txhua yam kev kho mob yog qhov tseem ceeb hauv txoj kev txiav txim siab kho mob, zam kev kho mob ntau dhau thiab tsis tsim nyog toxicity yuav tsum tau ua tib zoo xav. Hauv cov ntsiab lus no, ib pab pawg kws tshaj lij Portuguese tau koom nrog ntau lub rooj sib tham virtual uas muaj nyob nruab nrab ntawm Lub Ob Hlis thiab Plaub Hlis 2021, uas tau tsom los tshuaj xyuas cov pov thawj kho mob ntsig txog kev kho mob pem hauv ntej ntawm mRCC, nrog rau cov ntaub ntawv ntawm cov neeg mob uas TKI monotherapy yog. tseem yog qhov zoo tshaj plaws muaj kev kho mob. Cov ncauj lus uas suav tias muaj feem cuam tshuam rau qhov kev sib tham no raug tshuaj xyuas tom qab no, raws li cov lus xaus tseem ceeb los ntawm pawg kws tshaj lij no. Kab lus no yog ua raws li cov kev tshawb fawb yav dhau los thiab tsis muaj cov kev tshawb fawb tshiab nrog tib neeg koom lossis tsiaj ua los ntawm ib tus kws sau ntawv.
Tshuaj ntsuab Cistanche
THERAPEUTIC LANDSCAPE ntawm MRCC
Thawj cov neeg ua haujlwm raug pom zoo rau kev kho mRCC yog interferon-a thiab koob tshuaj IL-2. Txawm li cas los xij, txawm hais tias ua rau cov lus teb muaj zog heev hauv cov neeg mob tsawg, qhov ua tau zoo ntawm cov tshuaj no tau qis heev (cov lus teb tau tshaj tawm yog 12 feem pua rau interferon thiab 15 feem pua rau IL-2), thiab lawv cov toxicity yog siab heev. (tshwj xeeb tshaj yog ntawm IL-2) [5, 6, 19]. Yog li ntawd, tom qab ntawd lawv tau hloov pauv los ntawm cov phiaj xwm qhia ntawm ob qho tib si endothelium ntawm cov qog vasculature (cov tshuaj tiv thaiv VEGF) lossis ntawm cov qog cov kab mob oncogenic (mTOR inhibitors). Cov tshuaj tiv thaiv VEGF suav nrog qhov ncauj muaj TKIs tsom mus ncig VEGF nws tus kheej lossis nws cov receptors (axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib, sunitinib, thiab tivozanib), nrog rau cov tshuaj tiv thaiv kab mob VEGF hauv cov hlab ntsha (bevacizumab ua ke nrog {-}. 13}}a), whereas mTOR inhibitors suav nrog temsirolimus thiab everolimus [6, 19]. Tag nrho cov neeg ua haujlwm no tau pom tias muaj kev vam meej tsis muaj sia nyob (PFS) tau txais txiaj ntsig los ntawm kev hloov pauv uas twb muaj lawm thiab tau raug tshuaj xyuas ntau qhov chaw [20–22].
Tsis ntev los no, tau muaj kev txaus siab rau kev siv tshuaj tiv thaiv kab mob los kho cov neeg mob mRCC; cuam tshuam rau qhov pib tsis yog qhov tshwj xeeb, cov tswv yim kev tiv thaiv kab mob tsis ntev los no tau ua tiav cov phiaj xwm kev tiv thaiv kab mob tiv thaiv kab mob cuam tshuam nrog peripheral kam rau ua. Nivolumab, anti-programmed cell death 1 (PD-1) antibody uas xaiv thaiv kev cuam tshuam ntawm PD-1 thiab nws ligand (PD-L1), yog thawj ICI pom zoo nyob rau hauv qhov chaw no. Thaum piv nrog everolimus hauv cov neeg mob uas tau kho yav dhau los, nivolumab tau pom tias yuav txuas ntxiv OS (25. 16}}.57–{18}}.93; p {{20}}.002) thiab txhawm rau tshem tawm lub hom phiaj siab dua tus nqi teb (ORR 25 feem pua vs 5 feem pua ; odds ratio [OR] 5.98 ; 95% CI 3.68–9.72; p ＜0.001) [23].
Thaum kawg, qhov kev hloov pauv loj tau tshwm sim hauv mRCC kev kho mob armamentarium raws li kev sib koom ua ke ntawm ob tus neeg sawv cev tau qhia thiab, ntau zaus, hloov TKI monotherapy lub tswv yim raws li tus qauv kev saib xyuas (SOC). Ib qho ntawm cov kev sib txuas no suav nrog kev sib koom ua ke ntawm ob ICIs: nivolumab? ipilimumab (ib qho tshuaj tiv thaiv-CTL4 [cytotoxic T-lymphocyte-associated protein 4] antibody) [24–26]. Tseem, feem ntau ntawm cov kev kho ob zaug no suav nrog kev sib xyaw ntawm ICI nrog VEGF-targeted tshuaj: avelumab. axitinib [27], atezolizumab? bevacizumab [28], pembrolizumab? lenvatinib [29], pembrolizumab? axitinib [30, 31] thiab nivolumab? cabozantinib [32]. Qhov laj thawj tom qab lub tswv yim no yog kev tawm tsam ib txhij ntawm ob qhov tseem ceeb ntawm RCC qog: angiogenesis thiab kev tswj hwm kev tiv thaiv kab mob. Tseeb, los ntawm kev ua kom lub cev tiv thaiv kab mob thiab inhibit vasculature signaling nyob rau hauv cov qog microenvironment, cov tswv yim ua ke no yuav tsum, nyob rau hauv txoj kev xav, kov yeej cov kev txwv ntawm txhua yam tshuaj ib tus zuj zus, ua rau muaj kev tiv thaiv kab mob tiv thaiv kab mob tiv thaiv kab mob los ntawm kev hloov pauv zoo ntawm cov qog microenvironment [ 33, 34] ib.
1. International Guideline pom zoo cov tswv yim kho mob
Tau ntsib qhov chaw kho mob sai sai no, cov txheej txheem thoob ntiaj teb tau hloov kho los xav txog cov kev kho tshiab ua ke. Qee qhov kev sib txuas ua ke tau cog lus tseg, tab sis tseem tsis tau pom zoo vim tias lawv ua tsis tau raws li qhov tseem ceeb OS teeb liab (xws li avelumab ? axitinib thiab axitinib ? atezolizumab ). Txawm li cas los xij, lwm qhov kev sib txuas tau raug suav tias yog SOC tshiab hauv mRCC. Qhov tseeb, hauv qhov hloov tshiab tshaj tawm thaum lub Cuaj Hlis 2021, European Society for Medical Oncology (ESMO) pom zoo kom siv pembrolizumab. lenvatinib, pembrolizumab? axitinib los yog cabozantinib? nivolumab ua thawj kab kev kho mob rau txhua tus neeg mob uas muaj cov cell ntshiab mRCC, tsis hais lawv cov IMDC cov pab pawg muaj kev pheej hmoo (tag nrho cov lus pom zoo, qib I, A; ESMO-MCBS v1.1, qhab nia 4) [16]. Hauv cov neeg mob uas muaj kev pheej hmoo txaus ntshai ntawm IMDC, sunitinib lossis pazopanib yog lwm txoj hauv kev rau PD-1 inhibitor-raws li kev kho mob vim tias tsis muaj qhov zoo tshaj plaws ntawm PD-1 inhibitor-raws li kev sib txuas ntawm sunitinib hauv cov no. cov neeg mob, thiab cov txiaj ntsig zoo sib xws ntawm sunitinib thiab pazopanib hauv kev kawm COMPARZ [35] (theem I, B) [16].
Kev sib xyaw ua ke ntawm pembrolizumab? axitinib, cabozantinib? nivolumab thiab pembrolizumab? lenvatinib kuj tau pom zoo raws li qhov kev nyiam ua ntej rau txhua tus neeg mob nrog RCC raws li qhov hloov tshiab tshiab ntawm National Comprehensive Cancer Network cov lus qhia (nrog rau qeb 1 raws li cov pov thawj qib) [18]. Tsis tas li ntawd, nivolumab? ipilimumab kuj tseem suav tias yog qhov kev xaiv zoo tshaj plaws los kho cov neeg mob txom nyem- lossis nruab nrab-kev pheej hmoo nrog cov cell ntshiab mRCC. Txawm li cas los xij, cabozantinib monotherapy kuj tau lees paub tias yog kev kho mob tshwj xeeb rau cov neeg mob txom nyem-/ nruab nrab-kev pheej hmoo raws li lub koom haum no, nrog rau qib 2A pov thawj [18].
Thaum kawg, 2021 hloov tshiab ntawm European Association of Urology (EAU) cov lus qhia kuj tseem muab cov kev tiv thaiv kab mob sib xyaw ua ke ua lub luag haujlwm tseem ceeb hauv kev kho cov cell ntshiab mRCC, pom zoo rau pembrolizumab. axitinib, nivolumab? cabozantinib los yog pembrolizumab? lenvatinib raws li SOC rau txhua tus neeg mob uas muaj cov cell ntshiab mRCC, thiab cov nivolumab? ipilimumab kev sib xyaw ua ke hauv cov neeg txom nyem-/ nruab nrab-kev pheej hmoo ntawm cov neeg mob (tag nrho nrog 1b pov thawj qib) [17]. Raws li hauv ESMO cov lus qhia, TKI monotherapy raug tso tseg rau lwm txoj hauv kev rau cov neeg mob uas tsis tuaj yeem tau txais lossis zam rau ICIs.
Cistanche hmoov
2. Tam sim no pom zoo ua ke kev kho mob: Kev ua tau zoo thiab kev nyab xeeb Profile
Hauv seem no, peb tshuaj xyuas cov pov thawj tseem ceeb uas muaj nyob rau niaj hnub no hais txog kev siv cov kev sib txuas los kho cov cell ntshiab mRCC. Peb tsom rau nivolumab. ipilimumab, pembrolizumab? axitinib, nivolumab? cabozantinib thiab pembrolizumab? lenvatinib, uas tau pom zoo los ntawm peb lub koom haum tau hais ua ntej [16–18], thiab yog cov uas muaj cov pov thawj loj tshaj plaws.
Qhov kev tshawb fawb tseem ceeb uas ua rau pom zoo thiab cov lus pom zoo tom ntej ntawm nivolumab? ipilimumab yog CheckMate{{0}} [24–26]. Cov kws sau ntawv ntawm theem 3 qhov kev sim tshuaj ntsuam xyuas no tau txheeb xyuas qhov tshwm sim thiab kev nyab xeeb profile ntawm 1096 cov neeg mob uas yav tas los tsis tau kho cov cell mRCC, uas tau randomized kom tau txais nivolumab 3 mg / kg. ipilimumab 1 mg / kg txhua 3 lub lis piam rau plaub koob, ua raws li nivolumab 3 mg / kg txhua 2 lub lis piam, los yog sunitinib 50 mg ib hnub ib zaug hauv 6- lub lis piam mus (4 lub lis piam rau, 2 lub lis piam tawm ) [24–26] ib. Cov ntsiab lus tseem ceeb ntawm qhov kev sim no yog OS, ORR, thiab PFS hauv IMDC tau txiav txim siab nruab nrab-/cov neeg mob tsis zoo, uas suav nrog kwv yees li 77 feem pua ntawm cov neeg mob siab rau (ITT). Cov ntaub ntawv tawm tshiab tshaj tawm sib raug rau qhov nruab nrab ntawm kev ua raws li 55 lub hlis thiab ua kom pom qhov zoo tshaj ntawm nivolumab. ipilimumab tshaj sunitinib nyob rau hauv nruab nrab-/poor-risk pejxeem: qhov tseeb, txoj kev pheej hmoo ntawm kev tuag rau cov neeg mob nyob rau hauv lub caj npab sim yog 35 feem pua qis dua cov neeg mob nyob rau hauv lub caj npab tswj (HR {{40}} .65; 95 feem pua CI 0.54–{51}}.78) [26]. Ntxiv mus, txawm hais tias qhia txog qhov txiaj ntsig qeeb, PFS kuj tseem ntev dua hauv nivolumab. ipilimumab-kho cov neeg mob, nrog 4- xyoo yuav muaj peev xwm ntawm 32.7 feem pua vs 12.3 feem pua (HR 0.74; 95 feem pua CI {{60}}.62–0.88). Thaum kawg, ORR tau siab dua ntawm cov neeg mob hauv kev sim caj npab (41.9 feem pua vs 26.8 feem pua, p ＜0.0001), raws li qhov feem pua ntawm cov neeg mob ua tiav cov lus teb (10.4 feem pua vs 1.4 feem pua), thiab lub sijhawm teb (HR 0.45 ; 95% CI 0.31–0.65) [26].
Puas yog pembrolizumab? axitinib ua ke tau hais nyob rau hauv KEYNOTE {{0}} kev sim, uas suav nrog 861 kho-naı¨ve cov neeg mob uas muaj cov cell ntshiab mRCC [3{{20}}, 31] . Cov neeg mob no tau randomized kom tau txais pembrolizumab 200 mg ib zaug txhua 3 lub lis piam. axitinib 5 mg ob zaug ib hnub twg los yog sunitinib 50 mg ib hnub ib zaug hauv 6-lub lim tiam (4 lub lis piam rau, 2 lub lis piam tawm) [30, 31]. OS thiab PFS yog cov ntsiab lus tseem ceeb, thiab cov txiaj ntsig ntawm ob qho tib si txhawb nqa qhov zoo tshaj plaws ntawm kev kho mob sib xyaw piv nrog sunitinib. Nrog rau qhov nruab nrab ua raws li 30.6 lub hlis, HR rau OS yog 0.68 (95 feem pua CI 0.55–0.85; p=0.0003), thaum HR rau PFS yog 0.71 (95 feem pua CI 0.60–0.84; p \ 0.0001) [31]. Lub ORR hauv pembrolizumab? axitinib-kho cov neeg mob tau ntau dua li cov neeg mob uas tau kho sunitinib (60 feem pua vs 40 feem pua ; p \0.0001), raws li yog feem pua ntawm cov neeg mob uas muaj cov lus teb tiav (9 feem pua vs 3 feem pua) thiab lub sij hawm nruab nrab ntawm cov lus teb (23.5). vs 15.9 hli) [31].
CheckMate{0}}ER yog theem 3 kev soj ntsuam kuaj mob uas hais txog kev ua tau zoo thiab toxicity ntawm nivolumab. Kev sib xyaw ua ke ntawm cabozantinib [32] Luv luv, 651 cov neeg mob uas tsis tau kho cov cell mRCC yav dhau los tau randomized kom tau txais nivolumab 240 mg txhua 2 lub lis piam. cabozantinib 40 mg ib zaug ib hnub lossis sunitinib 50 mg ib hnub ib zaug hauv 6- lub lis piam mus (4 lub lis piam rau, 2 lub lis piam tawm) [32]. Tom qab kev soj ntsuam nruab nrab ntawm 18.1 lub hlis, thawj qhov kawg (PFS) tau ntsib, nrog qhov nruab nrab PFS ntawm 16.6 lub hlis ntawm cov neeg mob hauv caj npab sim piv rau 8.3 lub hlis hauv caj npab tswj (HR 0.51; 95; feem pua CI 0.41–{37}}.64; p \{45}}001). Kuj tseem muaj qhov sib txawv tseem ceeb hauv OS: qhov kev pheej hmoo ntawm kev tuag hauv nivolumab? cabozantinib-kho cov neeg mob tau 40 feem pua qis dua li cov neeg mob sunitinib-kho (HR 0.60; 98.89 feem pua CI, 0.40–0.89; p=0.001). Raws li, ORR tau tshaj tawm rau cov neeg mob hauv qhov kev sim caj npab yog siab dua li cov neeg mob hauv caj npab tswj (55.7 feem pua vs 27.1 feem pua ; p \ 0.001), raws li yog qhov ua tiav cov lus teb (8.0 feem pua vs 4.6 feem pua ) thiab lub sijhawm nruab nrab. ntawm teb (20.2 vs 11.5 lub hlis) [32].
Puas yog pembrolizumab? lapatinib ua ke tau raug soj ntsuam nyob rau hauv CLEAR sim ntawm 1069 cov neeg mob uas yav tas los tsis tau kho qhov tseeb cell mRCC [29]. Cov neeg mob tau randomized kom tau txais lenvatinib 20 mg ib hnub ib zaug. pembrolizumab 200 mg txhua 3 lub lis piam, lenvatinib 18 mg ib hnub twg? everolimus 5 mg ib zaug ib hnub, los yog sunitinib 50 mg ib hnub ib zaug hauv 6- lub lis piam mus (4 lub lis piam rau, 2 lub lis piam tawm) [29]. Tom qab kev soj ntsuam nruab nrab ntawm 26.6 lub hlis, qhov nruab nrab PFS (lub ntsiab lus kawg) tau ntev dua nrog pembrolizumab. lenvatinib versus sunitinib (23.9 vs 9.2 hli; HR 0.39; 95 feem pua CI 0.32–0.49; p \0.001). Pembrolizumab? lapatinib-kho cov neeg mob tau txhim kho OS piv rau cov neeg mob sunitinib-kho, nrog kev pheej hmoo ntawm kev tuag yog 34 feem pua qis dua nrog pembrolizumab. lenvatinib (HR 0.66; 95% CI 0.49–0.88; p=0.005). Piv nrog sunitinib, pembrolizumab? lapatinib tau txuam nrog ntau dua ORR (71.0 feem pua vs 36.1 feem pua ), ua tiav cov lus teb (16.1 feem pua vs 4.2 feem pua ), thiab lub sijhawm nruab nrab ntawm cov lus teb (25.8 vs 14.6 lub hlis) [29].
Txawm hais tias kev kho mob sib xyaw ua ke coj tau qhov txiaj ntsig tsis txaus ntseeg rau ntau tus neeg mob uas muaj cov cell ntshiab mRCC, lawv tau ua li ntawd ntawm tus nqi ntawm cov tshuaj lom ntau ntxiv piv nrog kev kho ib tus neeg sawv cev. Txawm hais tias qhov feem ntau ntawm cov tshuaj sunitinib-kho CheckMate-214 cov neeg mob raug kev txom nyem qib 3 lossis 4 kev kho mob ntsig txog cov xwm txheej tsis zoo (TRAEs) (64.1 feem pua vs 47.9 feem pua ntawm cov neeg mob kho nrog nivolumab ? ipilimumab), feem pua ntawm TRAEs ua rau kev txiav tawm yog siab dua hauv kev sim caj npab (22.7 feem pua vs 13.1 feem pua hauv kev tswj caj npab) [26]. Raws li rau KEYNOTE-426 mus sib hais, qhov tshwm sim ntawm TRAEs loj dua ntawm cov neeg mob kho nrog kev sib xyaw ua ke (28 feem pua vs 16 feem pua) [31]. Ntxiv mus, 21 feem pua , 20 feem pua , thiab 7 feem pua ntawm cov neeg mob hauv qhov kev sim caj npab txiav tawm pembrolizumab, axitinib, thiab ob qho tib si tshuaj, feem, vim tias muaj TRAEs, qhov feem pua ntawm cov neeg mob no yog 12 feem pua ntawm cov neeg mob sunitinib [31]. Hauv CheckMate-9ER, qib 3 lossis siab dua TRAEs tshwm sim hauv 60.6 feem pua ntawm cov nivolumab. cabozantinib-kho cov neeg mob thiab 50.9 feem pua ntawm cov neeg mob sunitinib-kho [32]. Tsis tas li ntawd, feem pua ntawm cov neeg mob uas tsis tau txais kev kho mob vim yog AEs yog 19.7 feem pua hauv kev sim caj npab (6.6 feem pua ntawm cov neeg mob txiav nivolumab nkaus xwb, 7.5 feem pua tshem cabozantinib nkaus xwb thiab 5.6 feem pua tshem tawm ob qho tib si), thiab 16.9 feem pua ntawm cov tswj caj npab [32. ]. Thaum kawg, hauv CLEAR, qhov tshwm sim ntawm qib 3 lossis siab dua TRAEs yog 71.6 feem pua nrog pembrolizumab. lenvatinib thiab 58.8 feem pua ntawm cov sunitinib, thiab AEs ua rau kev kho mob tsis tu ncua hauv 37.2 feem pua thiab 14.4 feem pua ntawm cov neeg mob, raws li [29].
Ob qhov kev tshuaj ntsuam xyuas meta tau ua tiav los daws cov tshuaj lom ntawm kev sib xyaw ua ke los ntawm kev xav thoob ntiaj teb. Ib qho ntawm lawv, los ntawm Quhal li al., suav nrog rau theem 3 kev sim thiab 5121 cov neeg mob, thiab suav nrog cov kev sib txuas hauv qab no: nivolumab? abilimumab, avelumab? axitinib, pembrolizumab? axitinib, atezolizumab? bevacizumab, nivolumab? cabozantinib thiab pembrolizumab? lenvatinib [36]. Thaum piv nrog cov neeg mob sunitinib-kho, cov neeg kho nrog nivolumab? ipilimumab muaj qhov ua tau zoo dua ntawm kev txiav kev kho mob vim yog TRAEs, thiab muaj hyperthyroidism, adrenal insufficiency, pneumonitis, colitis, thiab elevated alanine transaminase (ALT) thiab aspartate transaminase (AST). Ib yam li ntawd, pembrolizumab? axitinib kho cov neeg mob muaj qhov ua tau zoo dua ntawm kev muaj hyperthyroidism, adrenal tsis txaus, mob ntsws, mob plab, raws plab, mob tes taw, thiab nce qib ALT thiab AST. Nivolumab? cabozantinib-kho cov neeg mob muaj qhov ua tau zoo dua ntawm kev txiav kev kho mob vim yog TRAEs. Zoo sib xws, pembrolizumab? Cov neeg mob lapatinib-kho tau muaj qhov ua tau zoo dua ntawm kev kho mob tsis tu ncua vim TRAEs, thiab muaj hyperthyroidism, adrenal insufficiency, pneumonitis, raws plab, thiab nce qib AST. Nco ntsoov, thaum piv nrog sunitinib, tag nrho cov kev sib xyaw ua ke tau cuam tshuam nrog txo qis ntawm hematological adverse events (AEs) (namely neutropenia, anemia, thiab thrombocytopenia) [36].
Qhov thib ob meta-analysis, los ntawm Rizzo et al., tsom rau qhov tshwm sim ntawm plab hnyuv AEs thiab txiav txim siab 3059 cov neeg mob los ntawm plaub theem 3 kev sim, kho nrog sunitinib los yog ib qho ntawm cov kev sib txuas hauv qab no: pembrolizumab. axitinib, nivolumab? cabozantinib, avelumab? axitinib thiab pembrolizumab? lenvatinib [37]. Thaum piv nrog cov neeg mob sunitinib-kho, cov neeg kho nrog pembrolizumab? axitinib lossis pembrolizumab? lenvatinib muaj qhov ua tau zoo dua ntawm kev mob raws plab tag nrho, qib 3-4 raws plab, thiab qib 3-4 txo qis qab los noj mov. Tsis tas li ntawd, qhov tshwm sim ntawm kev mob raws plab txhua qib kuj tseem muaj ntau dua hauv nivolumab. cabozantinib-kho cov neeg mob. Qhov tshwm sim ntawm qib 3-4 xeev siab thiab txhua qib qis qab los noj mov yog siab dua nrog pembrolizumab. lenvatinib; Txawm li cas los xij, qhov tshwm sim ntawm txhua qib xeev siab tau qis dua nrog pembrolizumab. axitinib [37].
Cistanche tubulosa
3. Risk Stratification thiab nws cov kev cuam tshuam rau kev kho mob: Cov neeg mob uas muaj kev pom zoo
Tsuas yog nivolumab? ipilimumab, cov lus pom zoo los ntawm cov txheej txheem thoob ntiaj teb hais txog kev siv cov kev kho mob sib xyaw ua ke yog ywj siab ntawm cov neeg mob 'kev pheej hmoo prognostic. Qhov no yog vim tias thawj cov neeg ua tau zoo ntawm CheckMate-214 tsuas yog txwv rau cov neeg mob txom nyem-/ nruab nrab-kev pheej hmoo, thaum cov pej xeem ua tau zoo ntawm KEYNOTE-426 thiab CheckMate-9ER suav nrog cov neeg mob uas tau faib hauv tag nrho IMDC kev pheej hmoo qeb. Txawm li cas los xij, cov txiaj ntsig tau pom los ntawm cov neeg mob uas muaj kev pheej hmoo zoo thaum kho nrog kev kho mob sib xyaw ua ke zoo li me dua qhov pom los ntawm cov neeg nyob nruab nrab- lossis cov kev pheej hmoo tsis zoo, qee zaum tsis muaj qhov tseem ceeb hauv nws qhov kev sib piv nrog cov neeg mob sunitinib-kho. Cov qauv no zoo ib yam thoob plaws txhua qhov kev pom zoo ua ke, raws li qhia los ntawm kev txheeb xyuas tom qab hoc pooled [38] thiab raws li tau piav qhia luv luv hauv qab no rau txhua txoj kev tshawb fawb.
Hauv CheckMate{{{{1{13}}}}}}, 23 feem pua ntawm cov neeg mob muab faib rau txhua sab caj npab muaj kev pheej hmoo zoo (raws li txhais los ntawm IMDC prognostic qauv) [24, 25]. Txawm hais tias tsis suav nrog kev txheeb xyuas qhov ua tau zoo, cov neeg mob no txawm li cas los xij suav nrog ITT cov pej xeem thiab lawv cov txiaj ntsig tau txheeb xyuas. Cov pab pawg neeg soj ntsuam tau qhia txog qhov yuav luag sib tshooj ntawm OS thiab PFS txoj kev ciaj sia ntawm ob sab caj npab ntawm cov neeg mob uas muaj kev pheej hmoo: ntawm 48 lub hlis, 65.1 feem pua ntawm cov neeg mob tau muaj sia nyob hauv nivolumab. ipilimumab caj npab piv rau 68.9 feem pua hauv sunitinib caj npab (HR 0.93; 95 feem pua CI 0.62–1.40), thiab 25.4 feem pua vim 31.6 feem pua, feem, tsis tau nce qib (HR 1.84; 95 feem pua CI 1.29–2.6] OS thiab PFS cov txiaj ntsig ntawm cov neeg mob txaus ntshai uas tau kho nrog sunitinib yog cov lej zoo dua rau cov neeg kho nrog nivolumab. kev sib xyaw ua ke. Ntxiv mus, ORR ntawm 4 xyoo tau nce siab dua hauv cov neeg mob uas tau kho sunitinib (51.6 feem pua vs 29.6 feem pua ntawm cov caj npab sim, p=0.0005), txawm hais tias tus nqi ntawm cov lus teb ua tiav thiab lub sijhawm ntawm cov lus teb nyiam nivolumab. rooj tog [26]. Tsis tas li ntawd, ib qho kev soj ntsuam tom qab ntawm CheckMate -214 cov pej xeem stratified los ntawm IMDC cov xwm txheej muaj feem cuam tshuam tau pom tias ORR ntawm cov neeg mob uas tsis muaj kev pheej hmoo tsawg dua nrog nivolumab. ipilimumab dua nrog sunitinib (39 feem pua vs 50 feem pua) [39]. Tsis tas li ntawd, thaum ORR hauv cov neeg mob kho sunitinib txo qis zuj zus raws li tus naj npawb ntawm cov kev pheej hmoo nce ntxiv, ORR nrog nivolumab? ipilimumab yog kwv yees li qub rau txhua hom kev pheej hmoo ntawm tus neeg mob, qis dua me ntsis rau cov neeg mob hauv cov kev pheej hmoo txaus ntshai (39 feem pua vs 40-44 feem pua rau cov neeg mob uas muaj 1-6 qhov kev pheej hmoo) [39].
KEYNOTE{{0}} cov pej xeem suav nrog kwv yees li 31 feem pua ntawm cov neeg mob uas muaj kev pheej hmoo txaus ntshai, raws li tau hais los ntawm IMDC cov qauv [30, 31]. Raws li hauv CheckMate-214, OS nkhaus ntawm cov neeg mob no muaj cov qauv sib tshooj: ntawm 2 xyoos, 85.3 feem pua ntawm cov neeg mob kho nrog kev sib xyaw ua ke tseem muaj sia nyob, uas yog me ntsis qis dua 87.7 feem pua ntawm cov tshuaj sunitinib. cov neeg mob (HR 1.06; 95% CI 0.60–1.86; p=0.58) [31]. Hauv kev txheeb xyuas pawg ua ntej los ntawm IMDC cov kev pheej hmoo, cov txiaj ntsig OS tsuas yog tshwm sim hauv pawg nruab nrab-/poor-risk pawg (HR 0.63; 95 feem pua CI 0.50–0.81; p \ 0.001) [31]. Hauv PFS tsom xam los ntawm IMDC cov kev pheej hmoo, PFS cov txiaj ntsig nrog pembrolizumab? axitinib feem ntau zoo ib yam nyob rau hauv cov kev pheej hmoo, txawm hais tias cov txiaj ntsig hauv qeb muaj txiaj ntsig zoo tsis tau ncav cuag qhov tseem ceeb (HR 0.79; 95 feem pua CI 0.57–1.09; p=0.078). Txawm li cas los xij, ib qho kev soj ntsuam tom qab hoc pawg tau pom tias ORR tau txais txiaj ntsig nrog pembrolizumab? axitinib tau zoo ib yam thoob plaws txhua pawg IMDC kev pheej hmoo [31].
Kwv yees li ntawm 22 feem pua ntawm 651 tus neeg mob suav nrog hauv CheckMate-9ER tau muaj IMDC txhais tau tias muaj txiaj ntsig zoo [32]. Hauv kev txheeb xyuas pab pawg ua ntej los ntawm IMDC qeb kev pheej hmoo, cov neeg mob hauv pawg txaus ntshai-kev pheej hmoo muaj ciam teb tseem ceeb PFS txiaj ntsig nrog nivolumab. cabozantinib (HR 0.62; 95 feem pua CI 0.38–1.01), txawm hais tias qhov cuam tshuam HR tau siab dua li ntawm qhov kev pheej hmoo nruab nrab (HR {{16 }}.54; 95 feem pua CI 0.40–{24}}.72) thiab pluag-risk (HR 0.37; 95 feem pua CI 0 }.23–{31}}.58) pawg. Rau OS, tsis muaj txiaj ntsig zoo los ntawm nivolumab. cabozantinib nyob rau hauv qhov txaus ntshai txaus ntshai (HR 0.84; 95 feem pua CI 0.35–1.97) los yog intermediate-risk (HR 0.70; 95 feem pua CI 0.46–1.07) pawg, tab sis muaj txiaj ntsig OS tseem ceeb tau pom ntawm cov neeg mob hauv pawg neeg txom nyem (HR 0.37; 95 feem pua CI 0.21–0.66). Ntawm kev ceeb toom, thiab raws li tau tshaj tawm hauv KEYNOTE-426, puas yuav muaj ORR siab dua nrog nivolumab? cabozantinib piv rau sunitinib tau pom tsis tu ncua nyob rau hauv cov neeg mob nyob rau hauv kev txaus ntshai-kev pheej hmoo (los yog 25.9; 95 feem pua CI 9.8-40.2), intermediate-risk (OR 28.2; 95 feem pua CI 18.3-37.3), thiab pluag-risk (OR 30.5; 95 feem pua. CI 16.0–43.9) qeb [32].
Hauv txoj kev tshawb fawb CLEAR, kwv yees li 33 feem pua ntawm cov neeg mob tau nyob hauv pab pawg IMDC prognostic txaus ntshai [29]. Nyob rau hauv qhov kev ntsuam xyuas pab pawg ua ntej los ntawm IMDC cov kev pheej hmoo, PFS tau txais txiaj ntsig nrog pembrolizumab? lenvatinib tau pom nyob thoob plaws txhua pawg kev pheej hmoo, txawm hais tias HR tau siab dua me ntsis hauv pawg pab pawg muaj kev pheej hmoo (HR 0.41; 95 feem pua CI 0.28–{8}}.62) dua nyob rau hauv nruab nrab-kev pheej hmoo (HR 0.39; 95 feem pua CI 0.29–{16}}.52) los yog pluag-risk (HR 0.28; 95 feem pua CI 0.13–{24}}.60) pab pawg. Zoo ib yam li CheckMate-9ER, cov txiaj ntsig tseem ceeb ntawm OS tau pom nyob rau hauv pab pawg neeg txom nyem (HR 0.30; 95% CI 0.14–{{ 44}}.64), tab sis tsis yog nyob rau hauv qhov txaus ntshai-risk (HR 1.15; 95 feem pua CI 0.55–2.40) los yog nruab nrab-risk (HR 0.72; 95 feem pua CI 0.50–1.05) subgroups [29] .
Cistanche capsules
4. Tsis-Clear Cell RCC
Kev tswj xyuas kev kho mob ntawm cov neeg mob uas tsis paub meej ntawm tes RCC tseem yog qhov nyuaj tshwj xeeb. Raws li cov subtypes no tsis tshua muaj nyob rau hauv theem 3 kev sim, cov tswv yim kho mob ua haujlwm feem ntau yog ib qho ntxiv ntawm qhov tau soj ntsuam thiab pom zoo nyob rau hauv qhov chaw ntawm cov cell histology ntshiab. Txawm li cas los xij, cov txiaj ntsig ntawm cov neeg mob uas tsis paub meej cell RCC kho nrog kev pom zoo tam sim no cov kev kho mob raug txwv thiab feem ntau yog qhov qis dua rau cov neeg mob uas muaj cov cell ntshiab RCC. Kev lees paub qhov tseeb no, ob qho tib si National Comprehensive Cancer Network (NCCN) thiab EAU cov lus qhia pom zoo kom suav nrog cov neeg mob uas tsis muaj cell RCC hauv kev sim tshuaj thaum twg tsim nyog [17, 18]. Txawm li cas los xij, ob qho tib si ntawm cov koom haum no kuj pom zoo kom siv sunitinib, raws li cov ntaub ntawv los ntawm peb theem 2 qhov kev sim uas tau tshaj tawm qhov kev nyiam rau qhov zoo tshaj ntawm cov tshuaj tiv thaiv VEGF TKI piv nrog everolimus (ESPN [40], ASPEN [41] thiab RECORD. -3 [42] kev sim). NCCN cov lus qhia kuj pom zoo rau cabozantinib [18].
Cov txheej txheem ESMO muaj cov ncauj lus kom ntxaws ntxiv txog kev tswj hwm ntawm lub cell tsis meej RCC subtype [43]. Thaum lawv tuav cov lus pom zoo ntawm kev suav nrog cov neeg mob no hauv kev sim tshuaj tsim nyog, cabozantinib yog qhov kev xaiv thawj kab kev kho mob rau cov neeg mob papillary mRCC yam tsis muaj kev sim tshuaj ntxiv (theem II, B) [43]. Qhov kev sim SWOG PAPMET tau pom qhov txiaj ntsig PFS rau cabozantinib tshaj sunitinib (9.0 vs 5.6 lub hlis; HR 0.60; 95 feem pua CI 0.37–0.97 ; p=0.02) thiab siab dua ORR (23 feem pua vs 4 feem pua) [44]. Lwm txoj kev xaiv muaj xws li sunitinib (theem II, B) thiab pembrolizumab (theem III, B; raws li KeyNote-426 [30, 31]) yam tsis muaj kev sim tshuaj molecular ntxiv, thiab savolitinib hauv MET-driven qog, qhov twg muaj (qib III. , C; raws li SAVOIR sim [45]) [43]. Qhov tseeb, nyob rau hauv lub era ntawm precision oncology, cov txiaj ntsig tau taw qhia rau SOC hauv cov cell tsis meej RCC uas yuav, yav tom ntej, yuav raug kho raws li qhov tshwj xeeb histology nyob rau hauv pawg loj ntawm cov qog. Piv txwv li, nyob rau hauv cov neeg mob uas muaj papillary hom RCC, raws li tau hais los saum toj no, SWOG PAPMET Trial qhia txog qhov txiaj ntsig PFS nrog cabozantinib tshaj sunitinib [44], thaum savolitinib pom tau tias muaj txiaj ntsig zoo piv nrog sunitinib hauv txoj kev tshawb fawb SAVOIR [45], crizotinib pom muaj kab mob. tswj hauv CREATE [46] thiab foretinib qhia txog kev ua haujlwm antitumor hauv theem 2 txoj kev kawm [47]. Cov ntaub ntawv no qhia tias kev nyiam kev kho mob rau cov qog nqaij hlav tshwj xeeb no tuaj yeem hloov pauv yav tom ntej.
Hais txog kev sib xyaw ua ke hauv cov neeg mob uas tsis paub meej ntawm tes RCC, cov ntaub ntawv tseem tsis tshua muaj. Tib qhov kev sim tshwj xeeb tshwj xeeb rau cov xov tooj tsis meej RCC tau tshaj tawm los ntawm Gupta li al. [48]. Hauv txoj kev tshawb no, nivolumab? ipilimumab tau siv los kho cov neeg mob me me ntawm 18 tus neeg mob uas muaj ntau hom kab mob histological (papillary, chromophobe, tsis cais, lub raum adenocarcinoma, translocation, thiab medullary). Cov txiaj ntsig tau zoo tag nrho, nrog rau ORR ntawm 33.3 feem pua, qhov nruab nrab lub sijhawm teb ntawm 4.3 lub hlis, qhov nruab nrab PFS ntawm 7.1 lub hlis, thiab 12- hli OS ntawm 64.2 feem pua [48]. Txawm li cas los xij, cov txiaj ntsig no muaj lej zoo ib yam li cov uas tau siv los tiv thaiv VEGF TKIs. Ntxiv mus, qhov ua tau zoo ntawm qhov kev sib xyaw ua ke no tuaj yeem sib txawv nrog cov subtype ntawm cov xov tooj tsis meej RCC. Tachibana et al. Tsis ntev los no tau qhia txog qhov no los ntawm kev qhia cov nyhuv ntawm nivolumab. ipilimumab nyob rau hauv papillary RCC yog qhov qis dua qhov ua tau pom hauv cov neeg mob uas muaj cov cell ntshiab RCC, nrog qis ORR (14.2 feem pua vs 52.1 feem pua, p=0.06) thiab luv luv PFS (2.4 vs 28.1 lub hlis, p {{ 26}.014) [49]. Tsis tas li ntawd, Tykodi et al. Tsis ntev los no tau nthuav tawm cov txiaj ntsig nrog nivolumab. ipilimumab kev kho mob nyob rau hauv cov pej xeem ntawm cov neeg mob uas yav tas los tsis kho tsis meej cell mRCC [50]. Txawm hais tias raws li tus qauv me me (n=52), cov txiaj ntsig no tau zoo dua, qhia qhov nruab nrab PFS ntawm 3.7 lub hlis thiab qhov nruab nrab OS ntawm 21.2 lub hlis [50].
Rau tag nrho lwm cov kev sib txuas, qhov tsis txaus ntawm cov ntaub ntawv tiv thaiv cov lus pom zoo hauv qhov chaw tsis paub meej ntawm RCC. Yog li, raws li nws tam sim no sawv, xav txog ib txoj hauv kev nrog antiVEGF TKI monotherapy yuav muab cov txiaj ntsig tsis zoo nrog cov tshuaj lom tsawg dua li kev sib xyaw ua ke ntawm ICI.
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Mario Fontes-Sousa. Helena Magalha's. Alicia Oliveira: koj puas xav tau ntau tus thwjtim? Filipa Carneiro: koj puas xav tau ntau tus thwjtim? Filipa Palma dos Reis. Pedro Silvestre Madeira: koj puas xav tau ntau tus thwjtim? Sara Meireles
