Kansarka mindhicirka PD-1 / daawaynta PD-L1

Immunotherapy kansarka mindhicirka, immunotherapy kansarka malawadka, immunotherapy kansarka mindhicirka, iyo kansarka mindhicirka PD-1 / PD-L1 daawaynta.

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 kansarka mindhicirka 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 kansarka mindhicirka has increased from less than one year to 3 years, and 20% of patients can survive for 5 years or longer.

Sanadka 2020, maxaa ikhtiyaarro daaweyn ah oo cusub oo loo heli karaa bukaanada qaba kansarka mindhicirka malawadka? Waa maxay dawooyinka cusub ee u imanaya suuqa, Waaxda Caafimaadka ee Shabakada Caalamiga ah ee Oncologist ayaa soo uruurisay macluumaadkii ugu dambeeyay ee tixraacaaga.

Istaraatiijiyadda daaweynta daroogada Holistic ee kansarka mindhicirka ee horumarsan

1. Daaweynta-koowaad

Ikhtiyaarada daawaynta ee kansarka mindhicirka sare waxa ka mid ah daawaynta kiimoterabi, la beegsaday iyo immunotherapy. Kahor daaweynta, baaritaanka hidda-socodka waa in la sameeyaa, sababtoo ah dhakhtarku wuxuu samayn doonaa qorshe daaweyn oo ku salaysan meesha uu ku yaal nabarka asalka ah, isbeddellada hidde-socodka iyo ogaanshaha biomarker.

Kimistariga kansarka mindhicirka mindhicirka wuxuu doortaa isku darka daroogada badan. Dhakhaatiirtu waxay isku daraan oo u dhigmaan sida dhabta ah ee bukaanka. Nidaamka isku dhafka caadiga ah ee bilowga ah ee sida caadiga ah loo isticmaalo waa sida soo socota:

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

2. CAPEOX (Xeloda (Capecitabine) + Oxaliplatin)

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

4. FOLFOXIRI (LV / 5-fluorouracil + irinotecan + oxaliplatin)

Daawooyinkaan waxaa badanaa loo isticmaalaa Avastin® (bevacizumab) si loo wanaajiyo badbaadada, gaar ahaan daaweynta kansarka mindhicirka bidix.

Marka aan ka hadalno, waxaan sidoo kale u baahanahay inaan xusuusino qof walba in qorshaha daaweynta iyo saadaalinta burooyinka kansarka mindhicirka ee ku dhaca dhinaca bidix (hoos u soo dhaca xiidanka, xiidanka weyn ee 'sigmoid colon', malawadka) iyo dhinaca midig (koritaanka xiidanka, xiidanka sarreeyaa, cecum) ay gebi ahaanba ka duwan yihiin waana inaan lagu jahwareerin. Baadhista ka dib, qof walba waa inuu helaa khabiir awood u leh dejinta qorshe daaweyn.

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-

Qorshaha gaarka ah ee qeybta midig ee bukaanka nooca duurjoogta ee RAS / RAF waa sida soo socota. Heerka lagu taliyay ee aan qorsheeyay (doorbiday): FOLFOX / CapeOx / FOLFIRI ± bevacizumab; FOLFOXIRI ± bevacizumab. Marka la barbardhigo FOLFIRI + Avastin, heerka guud ee badbaadada 5-sano ee FOLFOXIRI + Avastin waxaa lagu qiyaasaa inuu laba-laabmay. Nidaamka lagu taliyay Class II: FOLFOX / FOLFIRI ± cetuximab.

2. Daaweynta safka labaad

Sadarka koowaad, waxaan u isticmaali doonnaa bevacizumab oo ay weheliso kiimiko ku daaweynta. Haddii daaweyntu aysan waxtar lahayn, waan beddeli karnaa nidaamka daaweynta kiimikada oo waxaan sii wadeynaa isticmaalka bevacizumab. Dabcan, sidoo kale waa suurtagal in la beddelo daroogo kale oo la bartilmaameedsaday isla waqtigaas sida daaweynta kemotherabi, loo beddelo abercept, ama ramucirumab.

3. Daaweynta saddexda iyo sadarka dambe

Doorashada safka koowaad iyo daawaynta safka labaad ee kansarka mindhicirka waa badiyaa qaar ka mid ah dawooyinka kemotherabi ee caadiga ah iyo daroogooyinka la beegsaday. Laga bilaabo daawaynta safka saddexaad waa daawaynta dhabarka. Qorshaha daawaynta ee dhabarka ayaa isticmaali kara dawooyinka kimotherabi ee afka laga qaato oo hadda soo baxay, oo ay ku jiraan TAS-102, iyo sidoo kale S-1 (tegio), rifafine, ama qaar ka mid ah difaaca jirka, sida pembrolizumab (MSI-H).

Horumarka daaweynta saxda ah ee loogu talagalay kansarka mindhicirka

Nooca '2017' ee tilmaamaha daaweynta kansarka mindhicirka, talooyinka ku saabsan baaritaanka hidde-wadaha kaliya waxay ku lug leeyihiin KRAS, NRAS, dMMR iyo MSI-H, iyo tilmaamaha ugu dambeeyay ee daaweynta ee 2020, bartilmaameedyada cusub sida BRAF, HER2, NTRK, iwm. cusub ee lagu daray Point, iyada oo loo marayo baaritaanka hidda-wadaha, si loo fahmo macluumaad badan oo kelli ku saabsan kansarka mindhicirka, ayaa naga caawin kara inaan helno xulashooyin daawooyin badan. Celceliska heerka badbaadada bukaanku waa in ka badan 3 sano, taas oo ah horumar weyn oo ay keeneen dawo sax ah.

1. Nooca noocee ah ayaa laga baarayaa bukaanjiifka kansarka mindhicirka?

Baadhitaanka ka dib, dhakhtarku waa inuu sameeyaa baaritaanka hidda-socodka ee bukaan kasta oo qaba kansarka mindhicirka mindhicirka (mCRC) sida ugu dhakhsaha badan ee suurtogalka ah si loo go'aamiyo koox-hoosaadka cudurka, maxaa yeelay macluumaadkani wuxuu saadaalin karaa saadaalinta daaweynta, sida HER2 kordhinta waxay soo jeedinaysaa anti-EGFR daaweynta caabbinta daroogada. Hidda-wadayaasha soo socda waa in la baaro

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

2. Bartilmaameedyada iyo daroogada la bartilmaameedsaday ee hada la daaweyn karo

VEGF: Bevacizumab, Apsip

VEGFR: ramucirumab, rigofinib, fruquintinib

EGFR: cetuximab, panitumumab

PD-1 / PDL-1: pamluzumab, nivolumab

CTLA-4: Ipilimumab

BRAF: Vimofinil, Connefini

NTRK: Larotinib

Liiska daawooyinka la bartilmaameedsaday iyo kuwa difaaca jirka ee loogu talagalay kansarka mindhicirka mindhicirka ee ilaa hadda laga oggolaaday gudaha iyo dibaddaba:

Tilmaamaha daroogada bartilmaameedka kansarka malawadka

Tilmaamaha bevacizumab waa : metastatic colorectal cancer and advanced, metastatic or recurrent kansarka sanbabada ee aan yareyn.

Tilmaamaha trastuzumab waa : HER2-positive metastatic breast cancer, HER2-positive early breast cancer, HER2-positive metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma patients.

Tilmaamaha Pertuzumab waa : This product is suitable for combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with high-risk recurrence of HER2-positive early kansarka naasaha.

Tilmaamaha Nivolumab waa : epidermal growth factor receptor (EGFR) gene mutation negative and anaplastic qanjiro 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).

Tilmaamaha regorafenib waa Bukaanka hore loogu daaweeyay kansarka mindhicirka ee metastatic. Durvalumab, Tremelimumab, Ipilimumab, iyo lapatini
b weli lagama heli karo Shiinaha.

Isbedelka hiddo-wadaha EGFR

Daawada cuncunka Epidermal factor receptor (EGFR) wuxuu ku dhacaa qiyaastii 10% kansarka mindhicirka weyn, badiyaa dhanka bidix.

Cetuximab iyo panitumumab waxaa si rasmi ah u ansixiyay FDA sanadihii 2004 iyo 2006 si loogu daaweeyo kansarka mindhicirka ee saxa ah.

Magaca daroogada: panitumumab (Vectibix)

Bartilmaameedka: EGFR

Soo-saare: Amgen (dibedda)

Tilmaamaha: EGFR kansarka mindhicirka mindhicirka, KRAS kansarka malawadka

Magaca daroogada: Cetuximab (Erbitux)

Bartilmaameedka: EGFR

Soo-saare: Merck (ka baxsan)

Indications: advanced colorectal cancer, kansarka madaxa iyo qoorta

Isbedelka hiddo-wadaha BRAF V600E

7-10% bukaannada kansarka mindhicirka weyn waxay wataan isbeddel BRAF V600E. Isbeddellada 'BRAF V600E' waa isbeddel ku shaqeeya BRAF waana nooc kala duwan oo leh saamiga ugu sarreeya ee BRAF.

Waxay leedahay astaamo caafimaad oo gaar ah:

Badanaa wuxuu ka muuqdaa xiidmaha midig;

Qiyaasta dMMR waa sarreysaa, oo gaareysaa 20%;

Saadaalinta xun ee isbeddelka BRAF V600E;

Habka wareejinta aan caadiga ahayn;

Bukaannada qaba hiddo-wadaha is-bedbeddelaya ee BRAF caadi ahaan waxay leeyihiin saadaal liita, qaar ka mid ah dawooyinka cusub ee ka hortagga kansarka ayaa la muujiyey inay labanlaabmaan waqtiga badbaadada.

Daraasadu waxay ogaatay in FOLFOXIRI + bevacizumab ay noqon karto daaweynta ugu fiican ee bukaanada qaba isbeddelada BRAF.

Tilmaamaha NCCN ee nooca V2 2019 waxay kugula talinayaan daaweynta khadka labaad ee kansarka mindhicirka mindhicirka ee BRAF V600E:

Verofenib + irinotecan + cetuximab / panitumumab

Dabarafenib + Trametinib + Cetuximab / Panitumumab

Encorafenib + Binimetinib + 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 Braftova second drug regimen the first targeted therapy approved by the FDA for patients with mCRC carrying BRAF mutations.

Isbedelka hiddo-wadaha Kras

KRAS kansarka mindhicirka nooca duurjoogta ah ayaa ah safka ugu horreeya ee xulashada isku-darka kiimoteraabiga la beegsaday, haddaba ikhtiyaar noocee ah ayaa loo doortaa kiimoteraabiga?

Intaad dooranaysid daroogo cayiman oo cayiman, waxaa lagugula talinayaa inaad doorato dawada kemotherabi oo leh OS dheer, taasi waa, cetuximab waa in lagu daraa FOLFOX, bevacizumabna waa in lagu daraa FOLFIRI. Xulashada gaarka ah ee qorshaha waxay u baahan tahay in lagu daro falanqaynta daaweynta gaarka ah:

Haddii ay jirto rajo daawo, cetuximab oo ay weheliso kemotherabi guud ahaan waa la door bidaa, maxaa yeelay waxtarka hadafka dhow ee cetuximab ayaa ka sareeya bevacizumab;

Bukaannada qaba cudurrada aan la daaweyn karin, bevacizumab oo ay weheliso kemotherabi ayaa loo isticmaali karaa safka koowaad, waxaana ku xigi kara cetuximab ama panitumumab.

Bukaannada qaba kansarka mindhicirka weyn waa in laga baaraa xaaladda isbadalka RAS oo ay ku jiraan KRAS iyo NRAS. Ugu yaraan xaaladda KRAS exon 2 waa in la go'aamiyaa.

Haddii xaaladuhu saamaxaan, KRAS exon 2 exon iyo heerka isbadalka NRAS ayaa loo baahan yahay in la cadeeyo.

Bevacizumab oo lagu daray laba-daawada kiimoterabi waxay u keeni kartaa PFS (badbaadada horu-kaca dhexdhexaadka ah) iyo OS (badbaadinta guud) faa'iidooyinka bukaannada leh isbeddellada KRAS.

Bukaannada qaba isbeddelada RAS, isticmaalka cetuximab wuxuu saameyn xun ku yeelan karaa guud ahaan waxtarka.

Bukaannada qaba isbeddelada KRAS ama isbedelada NRAS waa inaysan isticmaalin cetuximab ama panitumumab.

Kordhinta HER2

Kordhinta HER2 ama muujinta xad dhaafka ah waxaa laga helay 2% ilaa 6% bukaannada qaba kansarka mindhicirka weyn ee hormarsan ama kansarka leh.

Pertuzumab and trastuzumab combine with different HER2 domains to produce synergistic inhibition on buro unugyada.

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 daaweynta la beegsaday may benefit patients.

Isbedelka hidde-wadaha NTRK

Qiyaastii 1 ilaa 5% bukaannada kansarka mindhicirka weyn ayaa ku dhaca isugeynta 'NTRK fusion', iyo baaritaanka NGS ayaa lagula talinayaa.

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

Natiijooyinka baaritaanka waxay muujiyeen in heerka guud ee cafiska ee koox-hoosaadka kansarka caloosha iyo mindhicirka uu ahaa 43%, iyo heerka guud ee cafiska ee bukaannada kansarka mindhicirka uu ahaa 50%. Muddada jawaabta aad ayey u kala duwan tahay, laga bilaabo 3.5 bilood illaa in ka badan 14.7 bilood.

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.

Haweeney 75 jir ah oo qabta kansarka mindhicirka weyn (CRC) aad ayey u nasiib badan tahay:

Burooyinka aasaasiga ah ee xiidanka.

Kansarka xiidmaha

Beerka metastasis.

Entratinib 1600mg / m 2 waxaa afka lagu qaataa hal mar usbuucii hal mar usbuucii 4 maalmood oo isku xigta (yacni 4 maalmood / 3 maalmood oo nasasho ah), 28 maalmood oo kasta seddex isbuuc oo isku xigta. Ka dib sideed toddobaad oo daaweyn ah, nabarku si weyn ayuu u yaraaday.

Tijaabinta kansarka mindhicirka iyo tiknoolajiyada cusub

Amarka saadaalinta: MSI-H iyo BRAF nooca duurjoogta ah> MSI-H iyo mutant BRAF> MSS iyo BRAF nooca duurjoogta> MSS iyo BRAF mutant.

1. MSI-H / dMMR kansarka mindhicirka weyn

Xasilooni-darrada sare ee microsatelite-ka (MSI-H) waa cunsur wanaagsan, iyo heerka isbeddelka BRAF ee kansarka mindhicirka ee 'MSI-H' waa qiyaastii 50%.

Kahortagayaasha isbaarada kantaroolka jirka waa daaweyn waxtar u leh MSI-H. Xakameeyayaasha isbaarada difaaca jirka ee hadda khuseeya bukaanada qaba MSI-H nooca mCRC waxaa ka mid ah pembrolizumab, nivolumab, iyo ipilimumab.

Isku-darka Nivolumab / Ipilimumab wuxuu muujinayaa firfircooni xoog leh ee daaweynta safka hore

Isku-darka safka hore ee nivolumab (Opdivo) iyo ipilimumab (Yervoy) waxay muujiyeen faa iidooyin caafimaad oo muddo dheer soconaya bukaanada qaba kansarka mindhicirka mindhicirka (mCRC), buroodiisuna waa xasillooni darrada microsatelite (MSI-H) / Cilad hagaajinta cillad la'aanta (dMMR) -a FACP Heinz-Josef Lenz, MD, wuxuu yiri dadka qaba taariikhda saadaasha liidata.

Tijaabada Wajiga II CheckMate-142, cilmi baarayaashu waxay baareen nabadgelyada iyo waxtarka nivolumab oo lagu daray ipilimumab oo ah qiyaasta hoose ee daaweynta ugu horeysa ee bukaanka qaba MSI-H / dMMR mCRC (n = 45). Natiijooyinka hore ee lagu soo gudbiyey shirkii 2018 ESMO waxay muujisay in heerka jawaabta guud (ORR) ee bukaanada 45 ay ahayd 60%, iyo heerka xakamaynta cudurku uu ahaa 84%. Kulankii Sanadlaha ahaa ee ASCO ee 2019, cusbooneysiinta daaweynta ee tijaabada ayaa lagu dhawaaqay. Waqtiga la socoshada dhexdhexaadka ah ee 19.9 bilood, saamiga ORR ee isku dhafka uu qiimeeyay baaraha ayaa kordhay 64%, iyo 84% bukaanada ayaa xakameynaya cudurka weeks 12 toddobaad.

2. MSS kansarka malawadka

Horumar cusub oo ku yimid MSS kansarka mindhicirka mindhicirka: regorafen
ib (Stivarga) + nivolumab

Bukaanka qaba cudurka microsatellite stabilization (MSS), qiyaastii 53 bukaan ah ayaa la siiyay [isku darka daaweynta] waxayna gaareen heer jawaab celin sare ah 40%, taas oo aan hore loo arag qaybtan bukaan socodka diidan.

Waxaa jira xog joogto ah oo soo jeedinaysa in daaweynta anti-VEGF ay saameyn ku yeelan karto isku-xirnaanta PD-1. Hadda, tani waa markii ugu horreysay ee dadka ku dhex nool MSS. Marka la isku daro labadan istiraatiijiyadood ee daaweynta, waxaan aragnay natiijooyin aad u wanaagsan. Sidaa darteed, marka la isku daro istiraatiijiyadda ka hortagga VEGF iyo xakameynta isbaarada difaaca jirka, bukaanada qaba cudurka MSS waxay yeelan doonaan faa'iidooyin badbaado oo ballaaran.

Gabagabada Maqaalka

Waqtiga daaweynta la bartilmaameedsaday, bukaan kasta oo qaba kansarka mindhicirka mindhicirka waa inuu maraa ogaanshaha MSI, falanqaynta isbeddelka RAS iyo BRAF, oo wuxuu sameeyaa ballaadhinta HER2, NTRK iyo ogaanshaha hiddo-wadeyaasha kale inta suurtogalka ah. Baadhitaanka hidda-socodka (NGS) ayaa lagu dari doonaa weyn Heerka baaritaanka bilowga ah ee bukaanada badankood. Hadda bukaannada gudaha waxaa lagu tijaabin karaa Shabakadda Global Oncologist Network.

Waxaan ku nool nahay kacaankii meyroole ee daaweynta kansarka mindhicirka. Wax badan ayaan ka baranay genetik-ka hiddo-wadaha kansarka mindhicirka iyo sida loogu turjumo go'aannada daaweynta daaweynta. Wax badan ayaa jiri doona mustaqbalka. Sida ku saabsan horumarkii ugu dambeeyay ee cilmi baarista iyo qorshaha daaweynta ugu fiican ee kansarka mindhicirka, kaliya khubarada ugu sareysa kansarka ee gudaha iyo dibaddaba ayaa leh khibrad caafimaad oo hodan ah. Bukaannada kansarka mindhicirka mindhicirka waxay codsan karaan la-talin lala yeesho khabiiro awood leh iyada oo loo marayo Shabakadda Global Oncologist Network si ay u helaan qorshaha daaweynta ugu fiican.