Ciwon daji mai launi PD-1 / PD-L1

Immunotherapy ciwon daji na hanji, ciwon daji na dubura immunotherapy, ciwon daji na ciwon daji, da kuma ciwon daji PD-1 / PD-L1.

Shekaru goma sha bakwai da suka gabata, adadin magungunan da ake samu don ciwon daji mai ci gaba ya kasance mai iyaka. Akwai 'yan magungunan chemotherapeutic kuma kusan babu magungunan da aka yi niyya. Tare da haɓaka gwajin kwayoyin halitta da magungunan ciwon daji na zamani, marasa lafiya da aka gano tare da mataki na IV ciwon daji suna da ƙarin zaɓuɓɓukan magani. Wasu marasa lafiya na iya samun magani na asibiti, yayin da wasu na iya samun ƙarin niyya immunotherapy zažužžukan ta hanyar gwajin kwayoyin halitta, yana haifar da tsawon lokacin rayuwa. A halin yanzu, lokacin rayuwa na ci gaba maganin ciwon daji ya karu daga kasa da shekara guda zuwa shekaru 3, kuma 20% na marasa lafiya na iya rayuwa har tsawon shekaru 5 ko fiye.

A cikin 2020, waɗanne sababbin zaɓuɓɓukan magani suke akwai don marasa lafiya da ke fama da cutar kansa? Waɗanne sababbin magunguna ne ke zuwa kasuwa, Sashin Kiwon Lafiyar Jama'a na Oncologist Network ya tattara sabbin bayanai don tunatar da ku.

Dabarar maganin miyagun ƙwayoyi cikakke don ci gaba da ciwon kansa

1. Maganin farko

Zaɓuɓɓukan jiyya don ci-gaban ciwon daji na colorectal sun haɗa da chemotherapy, niyya da immunotherapy. Kafin magani, dole ne a gudanar da gwajin kwayoyin halitta, saboda likita zai yi tsarin kulawa bisa ga wurin da asalin cutar, maye gurbin kwayoyin halitta da gano kwayoyin halitta.

Kimiyyar sinadarai na kansar kai tsaye yakan zaɓi haɗin magunguna da yawa. Likitocin sun haɗu kuma sun dace daidai da ainihin halin mai haƙuri. Tsarin hadahadar daidaitaccen tsari wanda aka saba amfani dashi shine kamar haka:

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

2. CAPEOX (Xeloda (Capecitabine) + Oxaliplatin)

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

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

Wadannan magungunan ana amfani dasu galibi tare da Avastin® (bevacizumab) don inganta rayuwa, musamman don maganin cutar kansa ta hagu.

Da yake magana a kan wanna, ya kamata kuma mu tunatar da kowa cewa shirin magani da hangen nesa game da cututtukan daji da ke faruwa a gefen hagu (saukowa kan hanji, sigmoid colon, dubura) da gefen dama (hawan hawan, mai hawan mai kai, cecum) ya bambanta, kuma bai kamata a rude shi ba. Bayan ganewar asali, dole ne kowa ya nemi ƙwararren masani don tsara tsarin magani.

Takamaiman shirin don rabin hagu na RAS / RAF marasa lafiya na daji shine kamar haka. Shirin da aka ba da shawarar don Class I (wanda aka fi so): FOLFOX / FOLFIRI ± Cetuximab Class II shawarar da aka ba da shawarar: FOLFOX / CapeOx / FOLFIRI ± Bevacizumab; FOLFOXIRI ± Bevacizumab anti-

Tsarin takamaiman shirin na rabin rabin RAS / RAF marasa lafiya iri-iri kamar haka. Matakin shawarar da na tsara (wanda aka fi so): FOLFOX / CapeOx / FOLFIRI ± bevacizumab; FOLFOXIRI ± bevacizumab. Idan aka kwatanta da FOLFIRI + Avastin, kimanin shekaru 5 na FOLFOXIRI + Avastin an kiyasta sun ninka sau biyu. Tsarin shawarar II na II: FOLFOX / FOLFIRI ± cetuximab.

2. Maganin layi na biyu

A layin farko, zamuyi amfani da bevacizumab hade da chemotherapy. Idan jiyya ba ta da tasiri, za mu iya canza tsarin sanko da ci gaba da amfani da bevacizumab. Tabbas, yana kuma yiwuwa a canza wani magani da aka yi niyya a lokaci guda kamar tsarin maganin sankara, canza zuwa abercept, ko zuwa ramucirumab.

3. Layi na uku da layin baya

Zaɓin zaɓuɓɓukan magani na layi na farko da na biyu don ciwon daji na launin fata yawanci wasu ingantattun magungunan chemotherapy da magungunan da aka yi niyya. Farawa daga layi na uku magani ne na baya. Tsarin jiyya na baya na iya amfani da wasu magungunan chemotherapeutic na baka da suka fito, ciki har da TAS-102, da S-1 (tegio), rifafine, ko wasu immunotherapy, irin su pembrolizumab (MSI-H).

Cigaba a cikin daidaitaccen maganin da aka yi niyya don cutar kansa

A cikin yanayin 2017 na ka'idojin maganin cutar kansa, shawarwarin don gwajin kwayar halitta kawai sun haɗa da KRAS, NRAS, dMMR da MSI-H, kuma a cikin sabbin jagororin jiyya a cikin 2020, sabbin manufofi kamar BRAF, HER2, NTRK, da sauransu. sabon hade Point, ta hanyar gwajin kwayar halitta, don fahimtar karin kwayoyin kwayoyin cutar kansa, zai iya taimaka mana samun ƙarin zaɓuɓɓukan magani. Matsakaicin adadin rayuwar marasa lafiya ya fi shekaru 3, wanda shine babban ci gaban da aka samu ta hanyar daidaitaccen magani.

1. Wadanne kwayoyin halitta ne ya kamata a gwada wa masu fama da cutar kansa?

Bayan ganewar asirin, dole ne likita ya gudanar da gwajin kwayar halitta ga kowane mara lafiya da ke fama da cutar kansa (mCRC) da wuri-wuri don tantance rukuni-rukuni na cutar, saboda wannan bayanin na iya hango hangen nesa game da jiyya, kamar haɓakar HER2 yana nuna anti-EGFR magani Maganin juriya. Dole ne a gwada wadannan kwayoyin halitta!

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

2. Manufofi da magunguna masu niyya wanda za'a iya magance su a halin yanzu

VEGF: Bevacizumab, Apsip

VEGFR: ramucirumab, rigofinib, fruquintinib

EGFR: cetuximab, panitumumab

PD-1 / PDL-1: pamluzumab, nivolumab

CTLA-4: Ipilimumab

BRAF: Vimofinil, Connefini

NTRK: Larotinib

Jerin magungunan da aka yi niyya da magungunan rigakafi don cutar kansa wanda aka amince dashi har yanzu a gida da waje:

Nuni ga cututtukan daji da ke niyya ga magunguna

Alamomin bevacizumab sune : metastatic colorectal cancer da ci-gaba, metastatic ko maimaituwa cututtukan daji na kansa marasa kansar.

Alamomin trastuzumab sune : HER2-tabbatacce metastatic ciwon nono, HER2-tabbatacce farkon nono, HER2-tabbatacce metastatic ciki. adenocarcinoma ko gastroesophageal junction adenocarcinoma marasa lafiya.

Alamomin Pertuzumab sune : Wannan samfurin ya dace da haɗuwa tare da trastuzumab da chemotherapy a matsayin maganin adjuvant ga marasa lafiya tare da babban haɗari na sake dawowa na HER2-tabbatacce da wuri. ciwon nono.

Alamomin Nivolumab sune : Epidermal girma factor receptor (EGFR) maye gurbi mara kyau da anaplastic linzoma kinase (ALK) mara kyau, ci gaban cutar da ta gabata ko rashin jurewa a cikin gida ko haɓakawa bayan karɓar chemotherapy na tushen platinum Marasa lafiya marasa lafiya marasa kan gado (NSCLC).

Alamomin regorafenib sune : marasa lafiya tare da ciwon daji na launin fata na metastatic a baya. Durvalumab, Tremelimumab, Ipilimumab, da lapatini
b har yanzu ba a China.

Tsarin EGFR maye gurbi

Mai karɓar haɓakar haɓakar epidermal (EGFR) yana faruwa a cikin kusan 10% na ciwon daji na hanji, galibi akan hagu.

Cetuximab da panitumumab sun sami amincewar hukuma a FDA a 2004 da 2006 don maganin ciwan kansa mai saurin ciwan kansa.

Sunan magunguna: panitumumab (Vectibix)

Manufa: EGFR

Maƙerin: Amgen (a waje)

Manuniya: EGFR tabbatacce ciwon daji na fata, KRAS mummunan launi na rashin daidaito

Sunan magani: Cetuximab (Erbitux)

Manufa: EGFR

Maƙerin: Merck (a waje)

Alamomi: ci gaban ciwon daji na colorectal, kansar kai da wuya

BRAF V600E maye gurbi

7-10% na marasa lafiya na ciwon hanji suna ɗaukar maye gurbi na BRAF V600E. BRAF V600E maye gurbi shine BRAF mai kunna maye gurbi kuma shine bambancin da mafi girman yanayin BRAF.

Yana da halaye na musamman na asibiti:

Yafi bayyana a hannun dama na dama;

Matsakaicin dMMR ya yi yawa, ya kai 20%;

Rashin hangen nesa na maye gurbin BRAF V600E;

Yanayin canja wuri mara kyau;

Marasa lafiya tare da BRAF kwayoyin halitta yawanci suna da mummunan hangen nesa, kuma wasu sabbin takamaiman magungunan anti-cancer sun nuna an ninka lokacin rayuwa.

Binciken ya gano cewa FOLFOXIRI + bevacizumab na iya zama mafi kyawun magani ga marasa lafiya tare da maye gurbin BRAF.

Sharuɗɗan NCCN don sigar V2 2019 suna ba da shawarar yin maganin layi na biyu na cutar kansa mai saurin ɓarna ga BRAF V600E:

Verofenib + irinotecan + cetuximab / panitumumab

Dabarafenib + Trametinib + Cetuximab / Panitumumab

Encorafenib + Binimetinib + Cetux / Pan

Labari mai dadi shine cewa a gaban irin wannan haɗari na BRAF V600E mutant metastatic colorectal cancer, a ranar 8 ga Afrilu, 2020, Pfizer ya sanar da cewa FDA ta Amurka ta amince da Braftovi® (encorafenib, Cornefinil) da Erbitux® (cetuximab) , Cetuximab) a hade. tsarin magani (Braftovi na biyu magani tsarin), amfani da su bi da marasa lafiya da metastatic colorectal cancer (mCRC) dauke da BRAF V600E maye gurbi. Wadannan marasa lafiya sun riga sun karbi magani daya ko biyu. Wannan amincewa kuma yana sanya Braftova tsarin magani na biyu na farko da aka yi niyya wanda FDA ta amince da shi don marasa lafiya tare da mCRC dauke da maye gurbi na BRAF.

Kras gene maye gurbi

KRAS-irin ciwon daji na hanji shine farkon layin da aka zaba don haɗaɗɗiyar cutar sankara, don haka wane irin zaɓi ne na zaɓin magani don zaɓar?

Yayin da ake zaɓar wani magani da aka yi niyya, ana ba da shawarar zaɓar tsarin ƙarancin magani tare da dogon OS, ma'ana, ya kamata a haɗa cetuximab tare da FOLFOX, kuma bevacizumab ya kamata a haɗe shi da FOLFIRI. Takamaiman zaɓi na shirin yana buƙatar haɗuwa tare da takamaiman takamaiman asibiti:

Idan akwai fatan samun waraka, ana fifita cetuximab hade da chemotherapy gabaɗaya, saboda ƙimar makasudin kwanan nan ta cetuximab ya fi bevacizumab girma;

Ga marasa lafiya da ke fama da cutar da ba ta da magani, za a iya amfani da bevacizumab haɗe da chemotherapy a matsayin layi na farko, sannan cetuximab ko panitumumab.

Dole ne a gwada marasa lafiya da ke fama da cutar kansa don yanayin maye gurbin RAS ciki har da KRAS da NRAS. Akalla matsayin KRAS exon 2 yakamata a ƙaddara.

Idan yanayi ya ba da izinin, KRAS exon 2 exon da matsayin maye gurbi na NRAS suna buƙatar bayyana.

Bevacizumab haɗe tare da maganin chemotherapy biyu na iya kawo PFS (tsakanin ci gaba mara rayuwa) da fa'idodin OS (cikakken rayuwa) ga marasa lafiya tare da maye gurbin KRAS.

Ga marasa lafiya tare da maye gurbin RAS, amfani da cetuximab na iya haifar da mummunan tasiri akan ingancin gaba ɗaya.

Marasa lafiya tare da maye gurbin KRAS ko maye gurbin NRAS bai kamata suyi amfani da cetuximab ko panitumumab ba.

HER2 fadadawa

HER2 fadadawa ko nunawa da yawa an samo shi a cikin 2% zuwa 6% na marasa lafiya tare da ci gaba ko ƙananan cututtukan daji.

Pertuzumab da trastuzumab suna haɗuwa tare da yankuna daban-daban na HER2 don samar da hana haɗin gwiwa akan. tumo Kwayoyin.

Hanyara ita ce binciken farko na asibiti don bincika ingancin Pertuzumab + Trastuzumab far a cikin marasa lafiya tare da HER2 haɓakar ciwon daji na metastatic (ba tare da la'akari da matsayin maye gurbin KRAS ba). Wannan binciken ya nuna cewa HER2 dual-niyya far-Pertuzumab + Trastuzumab yana da jurewa da kyau, ko kuma ana iya amfani dashi azaman tsarin kulawa ga marasa lafiya tare da HER2 haɓakar ciwon daji na metastatic. Gwajin kwayoyin halittar farko don gano maye gurbi na HER2 da la'akari da fara amfani da HER2 Tarurrukan ci gaba zai iya amfanar marasa lafiya.

NTRK maye gurbi na maye gurbi

Kimanin 1 zuwa 5% na marasa lafiya na ciwon hanji suna haɓaka NTRK haɗuwa, kuma ana ba da shawarar gwajin NGS.

Daga Janairu 23 zuwa 25 ga Janairu, 2020, Societyungiyar Amurka ta Clinical Oncology Ciwon Gastrointestinal Taro (ASCO-GI) ya yi nazari na musamman game da tasirin magungunan asibiti na marasa lafiya tare da ciwace-ciwacen ƙwayoyi masu dauke da furotin na NTRK.

Sakamakon gwajin ya nuna cewa yawan gafarar da ake samu na karamin rukunin kansar ciki shine 43%, kuma yawan gafarar marasa lafiyar kansar shine 50%. Tsawan lokacin amsawa ya bambanta sosai, daga watanni 3.5 zuwa fiye da watanni 14.7.

Bayan tsaka-tsakin lokaci na watanni 19, matsakaicin lokacin rayuwa gabaɗaya ya kai watanni 33.4, kusan shekaru uku. Matsakaicin adadin tsira na shekara guda (OS) shine 69%. A lokacin yanke bayanan, hanji hudu masu ciwon daji da kuma pancreatic guda daya masu ciwon daji suna raye kuma yanayinsu bai yi tsanani ba. Kuma aminci da haƙuri na larotinib yana da kyau. Yawancin mummunan halayen sune aji 1 ko 2.

Wata mace mai shekaru 75 da ke fama da cutar sankarar sankara (CRC) ta yi sa'a sosai:

Ciwon ciki na farko.

Ciwon daji na Peritoneal.

Ciwon hanta.

Entratinib 1600mg / m 2 ana shan shi da baki sau ɗaya a mako sau ɗaya a mako don kwanaki huɗu a jere (watau kwanaki 4/4 kwanakin kashe), kowane kwana 3 na makonni uku a jere. Bayan makonni takwas na jiyya, raunin ya ragu sosai.

Magungunan rigakafin cututtukan kansa da sabon kayan ci gaba

Tsarin tsinkaye: MSI-H da BRAF nau'in daji> MSI-H da mutant BRAF> MSS da BRAF nau'in daji> MSS da Bantan mutant.

1. MSI-H / dMMR metastatic colorectal ciwon daji

Babban rashin zaman lafiya na microsatellite (MSI-H) shine kyakkyawan yanayin hangen nesa, kuma ƙimar canzawar BRAF a cikin cutar sankara ta cikin MSI-H kusan 50%.

Masu hana shingen shiga shinge magani ne mai tasiri ga MSI-H. Masu hana shingen bincike na rigakafi a halin yanzu suna amfani da marasa lafiya tare da nau'in MSC-H na mCRC sun hada da pembrolizumab, nivolumab, da ipilimumab.

Nivolumab / Ipilimumab haɗuwa yana nuna aiki mai ƙarfi a cikin maganin layi na farko

Haɗin haɗin layin gaba na nivolumab (Opdivo) da ipilimumab (Yervoy) ya nuna fa'ida mai ɗorewa ta asibiti mai ɗorewa ga marasa lafiya da ke fama da cutar sankarar hanji (mCRC), kuma kumburinsa shine rashin daidaiton microsatelite (MSI-H) / gyara rashin daidaituwa (dMMR) -a FACP Heinz-Josef Lenz, MD, ya ce mutanen da ke da mummunan tarihin hangen nesa.

A cikin gwaji na Phase II CheckMate-142, masu binciken sunyi nazarin aminci da ingancin nivolumab tare da ƙananan ipilimumab azaman maganin farko na marasa lafiya tare da MSI-H / dMMR mCRC (n = 45). Sakamakon da aka gabatar a taron na 2018 ESMO ya nuna cewa yawan mayar da martani (ORR) na marasa lafiya 45 shine 60%, kuma adadin cutar ya kasance 84%. A Taron shekara-shekara na 2019 ASCO, an sanar da ingantaccen asibiti na gwajin. A lokacin biyan biyan kuɗi na watanni 19.9, rabon ORR zuwa haɗakar da mai binciken ya tantance ya karu zuwa 64%, kuma 84% na marasa lafiya suna da ikon shawo kan cuta na weeks12 makonni.

2. Cutar sankara ta sankarau

Sabuwar nasara a cikin cutar ta sankara ta MSS: regorafen
ib (Stivarga) + nivolumab

Ga mai haƙuri tare da cutar microsatellite stabilization (MSS), game da marasa lafiya 53 sun sami [haɗin haɗin gwiwa] kuma sun sami saurin amsawa na 40%, wanda ba a taɓa ji ba a wannan ɓangaren marasa lafiya.

Akwai bayanai masu ɗorewa da ke nuna cewa maganin anti-VEGF na iya samun tasirin aiki tare da toshewar PD-1. Yanzu, wannan shine karo na farko tsakanin yawan MSS. Ta hanyar haɗa waɗannan dabarun maganin guda biyu, mun ga kyawawan sakamako. Sabili da haka, ta hanyar haɗa dabarun anti-VEGF tare da kawar da shingen bincike, marasa lafiya da cutar MSS za su sami fa'idodi masu girma.

Mataki na ƙarshe

A zamanin da ake niyya kan farfadowa, kowane mara lafiya da ke da cutar sankarau ya kamata ya wuce ganewar MSI, canjin yanayin maye gurbi na RAS da BRAF, kuma ya kara fadada HER2, NTRK da sauran gano kwayar halitta gwargwadon iko. Gwajin kwayar halitta (NGS) za a haɗa shi cikin manyan Tsarin gwajin farko na yawancin marasa lafiya. Yanzu ana iya gwada marasa lafiyar gida ta hanyar Global Oncologist Network.

Muna rayuwa ne a cikin juyin juya halin kwayar cutar kanjamau. Mun koyi abubuwa da yawa game da kwayar halittar kansar ta hanji da kuma yadda za a fassara ta a cikin shawarar maganin asibiti. Za a sami ƙari a nan gaba. Dangane da ci gaban bincike na baya-bayan nan da mafi kyawun shirin shan magani don ciwan kansa, manyan masana kansar a gida da waje suna da wadataccen ƙwarewar asibiti. Marasa lafiya na kansar kai tsaye na iya neman shawara tare da masana masu iko ta hanyar yanar gizo na Oncologist Network don samun mafi kyawun shirin magani.