Ukwelashwa komdlavuza we-colorectal PD-1 / PD-L1

Colon cancer immunotherapy, rectal cancer immunotherapy, colorectal cancer immunotherapy, and colorectal cancer PD-1 / PD-L1 treatment.

Seventeen years ago, the number of drugs available for advanced colorectal cancer was very limited. There were only a few chemotherapeutic drugs and almost no targeted drugs. With the development of genomic testing and sophisticated cancer drugs, patients diagnosed with stage IV umdlavuza colon have more and more treatment options. Some patients can achieve clinical cure, while others can obtain more targeted immunotherapy options through genetic testing, resulting in longer survival time. At present, the survival time of advanced umdlavuza colorectal has increased from less than one year to 3 years, and 20% of patients can survive for 5 years or longer.

Ngo-2020, yiziphi izindlela ezintsha zokwelashwa ezitholakalayo ezigulini ezinomdlavuza obomvu? Yimiphi imishanguzo emisha eza emakethe, i-Global Oncologist Network Medical Department ihlanganise imininingwane yakamuva oyisebenzisela yona.

Isu eliphelele lokwelashwa kwezidakamizwa lomdlavuza othuthukile wamakholoni

1. Ukwelashwa kolayini wokuqala

Treatment options for advanced colorectal cancer include chemotherapy, targeted and immunotherapy. Before the treatment, genetic testing must be carried out, because the doctor will make a treatment plan based on the location of the original lesion, genetic mutations and biomarker detection.

I-chemistry yomdlavuza obala ngokweqile imvamisa ikhetha ukuhlanganiswa kwezidakamizwa eziningi. Odokotela bahlangana futhi bahambisane ngokuya ngesimo sangempela sesiguli. Isikimu sokuhlanganiswa okujwayelekile esivame ukusetshenziswa kanjena:

1.I-FOLFOX (LV / 5-fluorouracil + oxaliplatin)

2.CAPEOX (Xeloda (Capecitabine) + Oxaliplatin)

3.I-FOLFIRI (LV / 5-fluorouracil + irinotecan)

I-FOLFOXIRI (LV / 4-fluorouracil + irinotecan + oxaliplatin)

Lezi zindlela zokwelapha zivame ukusetshenziselwa ukuhambisana ne-Avastin® (bevacizumab) ukwenza ngcono ukusinda, ikakhulukazi ekwelashweni komdlavuza wamakholoni wesobunxele.

Uma sikhuluma ngalokhu, sidinga futhi ukukhumbuza wonke umuntu ukuthi uhlelo lokwelashwa kanye nokubikezelwa kwamathumba omdlavuza we-colorectal okwenzeka ohlangothini lwesobunxele (ukwehla kwekholoni, i-sigmoid colon, i-rectum) nohlangothi lwangakwesokudla (i-colon ekhuphukayo, i-colon eguqukayo, i-cecum) ihluke ngokuphelele, futhi akufanele idideke. Ngemuva kokuxilongwa, wonke umuntu kumele athole uchwepheshe onegunya lokwenza uhlelo lokwelashwa.

The specific plan for the left half of RAS / RAF wild-type patients is as follows. The recommended plan for Class I (preferred): FOLFOX / FOLFIRI ± Cetuximab Class II recommended plan: FOLFOX / CapeOx / FOLFIRI ± Bevacizumab; FOLFOXIRI ± Bevacizumab anti-

Uhlelo oluthile lwesigamu esifanele seziguli zohlobo lwe-RAS / RAF lumi kanje. Izinga eliphakanyisiwe engilihlelayo (engilithandayo): FOLFOX / CapeOx / FOLFIRI ± bevacizumab; I-FOLFOXIRI ± bevacizumab. Uma kuqhathaniswa ne-FOLFIRI + Avastin, isilinganiso sokusinda seminyaka emihlanu se-FOLFOXIRI + Avastin kulinganiselwa ukuthi siphindwe kabili. Uhlobo lwe-Class II olunconyiwe: I-FOLFOX / FOLFIRI ± cetuximab.

2. Ukwelashwa kolayini wesibili

Kulayini wokuqala, sizosebenzisa i-bevacizumab ehlangene ne-chemotherapy. Uma ukwelashwa kungasebenzi, singashintsha i-chemotherapy regimen bese siqhubeka nokusebenzisa i-bevacizumab. Vele, kungenzeka futhi ukuthi ushintshe omunye umuthi ohlosiwe ngasikhathi sinye nohlobo lwemithi yokwelashwa ngamakhemikhali, ukushintshela ku-abercept, noma i-ramucirumab.

3. Ukwelashwa kolayini besithathu nabasemuva

The choice of first-line and second-line drug options for colorectal cancer is usually some relatively standard chemotherapy drugs and targeted drugs. Starting from the third-line treatment is a back-line treatment. The back-line treatment plan can use some oral chemotherapeutic drugs that have just come out, including TAS-102, as well as S-1 (tegio), rifafine, or some immunotherapy, such as pembrolizumab (MSI-H).

Ukuthuthuka ekwelashweni okuqondiswe ngqo komdlavuza onobala

Kunguqulo ye-2017 yemihlahlandlela yokwelashwa komdlavuza omhlophe, izincomo zokuhlolwa kofuzo zifaka kuphela i-KRAS, NRAS, dMMR neMSI-H, nakwiziqondiso zakamuva zokwelashwa ngo-2020, imigomo emisha efana neBRAF, HER2, NTRK, njll. iPhoyinti esanda kufakwa, ngokuhlolwa kofuzo, ukuqonda imininingwane eyengeziwe yamangqamuzana omdlavuza obala, kungasisiza ekutholeni izinketho zemithi ethe xaxa. Izinga lokusinda eliphakathi kweziguli lingaphezu kweminyaka emi-3, okuyinqubekela phambili enkulu elethwe umuthi wokunemba.

1. Yiziphi izakhi zofuzo okufanele zihlolwe iziguli ezinomdlavuza onemibala egqamile

Ngemuva kokuxilongwa, udokotela kufanele ahlole ukuhlolwa kofuzo kwesiguli ngasinye esinomdlavuza we-metastatic colorectal (mCRC) ngokushesha okukhulu ukuze kunqunywe iqembu elincane lalesi sifo, ngoba lolu lwazi lungaqagela ukubikezelwa kokwelashwa, njengokukhuliswa kwe-HER2 kusikisela ukuthi i-anti-EGFR ukwelashwa Ukumelana nezidakamizwa. Izakhi zofuzo ezilandelayo kufanele zihlolwe!

I-MSI, BRAF, KRAS, NRAS, RAS, HER2, NTRK.

2. Okuqondiwe nezidakamizwa eziqondisiwe ezingalashwa njengamanje

I-VEGF: Bevacizumab, i-Apsip

I-VEGFR: i-ramucirumab, i-rigofinib, i-fruquintinib

I-EGFR: i-cetuximab, i-panitumumab

PD-1 / PDL-1: pamluzumab, nivolumab

I-CTLA-4: Ipilimumab

IBRAF: IVimofinil, iConnefini

I-NTRK: Larotinib

Uhlu lwezidakamizwa ezihlosiwe kanye ne-immunotherapy zomdlavuza obala wamukelwe kuze kube manje ekhaya nakwamanye amazwe:

Izinkomba zemithi ehlosiwe yomdlavuza obala kakhulu

Izinkomba ze-bevacizumab yilezi : metastatic colorectal cancer and advanced, metastatic or recurrent umdlavuza wamaphaphu weselula ongewona omncane.

Izinkomba ze-trastuzumab yilezi : HER2-positive metastatic breast cancer, HER2-positive early breast cancer, HER2-positive metastatic gastric i-adenocarcinoma or gastroesophageal junction adenocarcinoma patients.

Izinkomba zePertuzumab yilezi : This product is suitable for combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with high-risk recurrence of HER2-positive early umdlavuza webele.

Izinkomba zeNivolumab yilezi : epidermal growth factor receptor (EGFR) gene mutation negative and anaplastic i-lymphoma kinase (ALK) negative, previous disease progression or intolerable locally advanced or metastatic after receiving platinum-based chemotherapy Adult patients with non-small cell lung cancer (NSCLC).

Izinkomba ze-regorafenib yilezi : patients with previously treated metastatic colorectal cancer. Durvalumab, Tremelimumab, Ipilimumab, and lapatini
b ayikatholakali eChina.

Ukuguqulwa kwezakhi zofuzo ze-EGFR

I-Epidermal growth factor receptor (EGFR) ivela cishe ku-10% womdlavuza we-colon, imvamisa kwesobunxele.

I-Cetuximab ne-panitumumab zamukelwa ngokusemthethweni yi-FDA ngo-2004 nango-2006 ekwelapheni umdlavuza osezingeni eliphezulu.

Igama lomuthi: panitumumab (Vectibix)

Okuqondiwe: EGFR

Umkhiqizi: Amgen (ngaphandle)

Izinkomba: Umdlavuza omuhle we-EGFR, umdlavuza we-KRAS ongemuhle

Igama lomuthi: Cetuximab (Erbitux)

Okuqondiwe: EGFR

Umkhiqizi: Merck (ngaphandle)

Indications: advanced colorectal cancer, umdlavuza wekhanda nentamo

Ukuguqulwa kwezakhi zofuzo kwe-BRAF V600E

I-7-10% yeziguli zomdlavuza wekoloni zithwala ukuguqulwa kwe-BRAF V600E. Ukuguqulwa kwe-BRAF V600E kungukushintsha kwe-BRAF okusebenzayo futhi okuhlukile ngenani eliphakeme kakhulu le-BRAF.

Inezici ezihlukile zomtholampilo:

Ikakhulu ivela kukholoni elungile;

Inani le-dMMR liphezulu, lifinyelela kuma-20%;

Isibikezelo esibi sokuguqulwa kwezakhi ze-BRAF V600E;

Imodi yokudlulisa ye-Atypical;

Iziguli ezinezakhi zofuzo eziguqukayo ze-BRAF zivame ukuba nesibikezelo esibi, kanti eminye imishanguzo emisha elwa nomdlavuza ikhonjiswe isikhathi sokuphila okuphindwe kabili.

Ucwaningo luthole ukuthi i-FOLFOXIRI + bevacizumab ingaba ukwelashwa okungcono kakhulu kweziguli ezinezinguquko ze-BRAF.

Imihlahlandlela ye-NCCN yenguqulo V2 2019 incoma ukwelashwa komugqa wesibili komdlavuza we-metastatic colorectal we-BRAF V600E:

I-Verofenib + irinotecan + cetuximab / panitumumab

UDabarafenib + Trametinib + Cetuximab / Panitumumab

Encorafenib + IBinimetinib + Cetux / Pan

The good news is that in the face of such a dangerous BRAF V600E mutant metastatic colorectal cancer, on April 8, 2020, Pfizer announced that the US FDA has approved Braftovi® (encorafenib, Cornefinil) and Erbitux® (cetuximab) , Cetuximab) combined drug regimen (Braftovi second drug regimen), used to treat patients with metastatic colorectal cancer (mCRC) carrying BRAF V600E mutation. These patients have already received one or two pre-treatments. This approval also makes the UBraftovi second drug regimen the first targeted therapy approved by the FDA for patients with mCRC carrying BRAF mutations.

Ukuguqulwa kohlobo lwe-Kras

Umdlavuza we-colon we-KRAS wasendle uyindlela yokuqala yokwelashwa oyithandayo yenhlanganisela ehlosiwe yamakhemikhali, ngakho-ke hlobo luni lwenketho ye-chemotherapy ongayikhetha?

Ngenkathi ukhetha umuthi othile ohlosiwe, kunconywa ukuthi ukhethe uhlobo lwe-chemotherapy nge-OS ende, okungukuthi, i-cetuximab kufanele ihlanganiswe ne-FOLFOX, futhi i-bevacizumab kufanele ihlanganiswe ne-FOLFIRI. Inketho ethile yohlelo idinga ukuhlanganiswa nokuhlaziywa okuqondile komtholampilo:

Uma kukhona ithemba lokwelashwa, i-cetuximab ehlangene ne-chemotherapy ngokuvamile iyathandwa, ngoba ukusebenza kwenjongo ye-cetuximab kuphakeme kune-bevacizumab;

Ezigulini ezinesifo esingelapheki esithuthukile, i-bevacizumab ehlanganiswe ne-chemotherapy ingasetshenziswa njengomugqa wokuqala, ilandelwe yi-cetuximab noma i-panitumumab.

Iziguli ezinomdlavuza we-colon we-metastatic kufanele zihlolwe isimo sokuguqulwa kwe-RAS kufaka phakathi i-KRAS ne-NRAS. Okungenani isimo se-KRAS exon 2 kufanele sinqunywe.

Uma izimo zivuma, i-KRAS exon 2 exon nesimo sokuguquka kwe-NRAS kudinga ukucaciswa.

I-Bevacizumab ehlanganiswe nokwelashwa ngamakhemikhali kwezidakamizwa ezimbili kungaletha izinzuzo ze-PFS (ukusinda okumaphakathi) kanye ne-OS (ukusinda kukonke) ezigulini ezinokuguqulwa kwe-KRAS.

Ezigulini ezinezinguquko ze-RAS, ukusetshenziswa kwe-cetuximab kungaba nomthelela omubi ekusebenzeni okuphelele.

Iziguli ezinokuguqulwa kwe-KRAS noma ukuguqulwa kwe-NRAS akufanele zisebenzise i-cetuximab noma i-panitumumab.

Ukukhulisa i-HER2

Ukukhuliswa kwe-HER2 noma i-overexpression kutholakale ku-2% kuya ku-6% yeziguli ezinomdlavuza ophakeme noma we-metastatic colorectal.

Pertuzumab and trastuzumab combine with different HER2 domains to produce synergistic inhibition on isisu amaseli.

My Pathway is the first clinical study to explore the efficacy of Pertuzumab + Trastuzumab therapy in patients with HER2 amplified metastatic colorectal cancer (regardless of KRAS mutation status). This study shows that HER2 dual-targeted therapy-Pertuzumab + Trastuzumab is well tolerated, or may be used as a treatment plan for patients with HER2 amplified metastatic colorectal cancer. Early genetic testing to identify HER2 mutations and consider early use of HER2 ukwelashwa okubhekiswe may benefit patients.

I-NTRK gene fusion mutation

Cishe i-1 kuya ku-5% yeziguli zomdlavuza wekoloni zithuthukisa ukuhlanganiswa kwe-NTRK, futhi kunconywa ukuhlolwa kwe-NGS.

From January 23 to January 25, 2020, the American Society of Clinical Oncology I-Tumor Yesisu Symposium (ASCO-GI) specifically analyzed the clinical drug effects of patients with gastrointestinal tumors carrying NTRK fusion protein.

Imiphumela yokuhlolwa ikhombise ukuthi inani eliphelele lokuxolelwa kweqembu elincane lomdlavuza wamathumbu lalingama-43%, kanti izinga lokuxolelwa kweziguli ezinomdlavuza wamakholoni lalingama-50%. Isikhathi sokuphendula sehluka kakhulu, sisuka ezinyangeni eziyi-3.5 kuye ngaphezu kwezinyanga eziyi-14.7.

After a median follow-up period of 19 months, the median overall survival time was up to 33.4 months, nearly three years. The one-year overall survival rate (OS) is 69%. At the time of the data cutoff, four colon cancer patients and one pancreatic cancer patient were still alive and their condition did not deteriorate. And the safety and tolerability of larotinib is good. Most adverse reactions are grade 1 or 2.

Owesifazane oneminyaka engama-75 ubudala onomdlavuza we-metastatic colorectal (CRC) unenhlanhla enkulu:

Isigaxa esiyinhloko samakholoni.

Umdlavuza wePeritoneal.

Isibindi se-metastasis.

I-Entratinib 1600mg / m 2 yathathwa ngomlomo kanye ngesonto kanye ngeviki ngezinsuku ezi-4 ezilandelanayo (okungukuthi izinsuku ezi-4 / izinsuku ezi-3 zokuphumula), njalo ezinsukwini ezingama-28 amasonto amathathu alandelanayo. Ngemuva kwamasonto ayisishiyagalombili ekwelashwa, lesi sifo sancipha kakhulu.

I-Colorectal cancer immunotherapy kanye nokusungulwa okusha kwempahla

Ukuhleleka kokubikezela: Uhlobo lwasendle lwe-MSI-H ne-BRAF> i-MSI-H ne-BRAF mutant> uhlobo lwe-MSS ne-BRAF zasendle> i-MSS ne-BRAF mutant.

1. Umdlavuza we-MSI-H / dMMR we-metastatic colorectal

Ukungazinzi okuphezulu kwe-microsatellite (MSI-H) kuyinto enhle yokubikezela, futhi izinga lokuguqulwa kwe-BRAF kumdlavuza we-MSI-H ongaba ngu-50%.

Ama-immune checkpoint inhibitors ayindlela yokwelapha esebenzayo ye-MSI-H. Ama-immune checkpoint inhibitors njengamanje asebenza ezigulini ezinohlobo lwe-MSI-H mCRC afaka phakathi i-pembrolizumab, nivolumab, ne-ipilimumab.

Inhlanganisela yeNivolumab / Ipilimumab ikhombisa umsebenzi oqinile ekwelashweni komugqa wokuqala

Inhlanganisela engaphambili ye-nivolumab (Opdivo) ne-ipilimumab (Yervoy) ikhombise inzuzo eqinile futhi ehlala isikhathi eside ezigulini ezinomdlavuza we-metastatic colorectal (mCRC), kanti isimila sayo ukungazinzi kwemicrosatellite (MSI-H) / mismatch repair Defect (dMMR) - i-FACP uHeinz-Josef Lenz, MD, uthe abantu abanomlando omubi wokubikezela.

Esivivinyweni seSigaba II se-CheckMate-142, abacwaningi bahlole ukuphepha nokusebenza kwe-nivolumab kanye ne-low-dose ipilimumab njengokwelashwa komugqa wokuqala kweziguli ezine-MSI-H / dMMR mCRC (n = 45). Imiphumela yangaphambilini ethunyelwe engqungqutheleni ye-ESMO yowezi-2018 ikhombise ukuthi izinga eliphelele lokuphendula (ORR) leziguli ezingama-45 lalingama-60%, kanti izinga lokulawulwa kwezifo lalingu-84%. Emhlanganweni Wonyaka we-2019 ASCO, kwamenyezelwa ukuvuselelwa komtholampilo kwecala. Ngesikhathi sokulandelela okuphakathi kwezinyanga eziyi-19.9, isilinganiso se-ORR nenhlanganisela ehlolwe umphenyi senyuke safinyelela kuma-64%, kanti iziguli ezingama-84% zazilawula izifo amasonto ayi -12.

2. Umdlavuza omkhulukazi weMSS

Ukuqhamuka okusha komdlavuza obala weMSS: regorafen
ib (Stivarga) + nivolumab

Esigulini esinesifo se-microsatellite stabilization (MSS), cishe iziguli ezingama-53 zathola [i-combination therapy] futhi zathola izinga eliphezulu lokuphendula elingu-40%, okungazwakali kule ngxenye yeziguli eziphikisayo.

Kunemininingwane eqhubekayo ephakamisa ukuthi ukwelashwa kwe-anti-VEGF kungaba nomthelela wokusebenzisana ne-PD-1 blockade. Manje, lesi yisikhathi sokuqala phakathi kwabantu beMSS. Ngokuhlanganisa lezi zindlela ezimbili zokwelashwa, sibone imiphumela ehlaba umxhwele kakhulu. Ngakho-ke, ngokuhlanganisa amasu we-anti-VEGF nokucindezela amasosha omzimba, iziguli ezinesifo se-MSS zizoba nezinzuzo ezinkulu zokusinda.

Isiphetho sendatshana

Ngenkathi yokwelashwa okuhlosiwe, sonke isiguli esinomdlavuza obala ngokobulili kufanele sidlule ukutholwa kwe-MSI, ukuhlaziywa kwezinguquko kwe-RAS ne-BRAF, futhi senze ukukhuliswa kwe-HER2, i-NTRK nokunye ukutholwa kofuzo ngangokunokwenzeka. Ukuhlolwa kofuzo (NGS) kuzofakwa enkulu Izinga lokuqala lokuhlolwa kweziguli eziningi. Manje iziguli ezifuywayo sezingahlolwa nge-Global Oncologist Network.

Siphila ekuguqulweni kwamangqamuzana ekwelashweni komdlavuza obala ngamabele. Sifunde okuningi mayelana nezakhi zofuzo zamangqamuzana zomdlavuza wamakholoni nokuthi uwahumushela kanjani ezinqumweni zokwelashwa zokwelashwa. Kuzoba nokuningi ngokuzayo. Ngokuqondene nenqubekela phambili yocwaningo lwakamuva kanye nohlelo lwemithi oluhamba phambili lomdlavuza omnyama, ochwepheshe abaphezulu kuphela bomdlavuza ekhaya nakwamanye amazwe abanolwazi olucebile lomtholampilo. Iziguli ezinomdlavuza ocacile zingafaka izicelo zokubonisana nochwepheshe abanegunya ngeGlobal Oncologist Network ukuthola uhlelo lokwelashwa olungcono kakhulu.