Colon cancer immunotherapy, rectal cancer immunotherapy, colorectal cancer immunotherapy, uye colorectal cancer PD-1 / PD-L1 kurapwa.
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 kenza yemaroni 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 kenza yakajeka has increased from less than one year to 3 years, and 20% of patients can survive for 5 years or longer.
Muna 2020, ndedzipi nzira nyowani dzekurapa dziripo kune varwere vane kenza yakajeka? Ndeapi mishonga mitsva iri kuuya kuzotengesa, iyo Global Oncologist Network Medical Dhipatimendi yakanyora ruzivo rwechizvino-zvino kuti ureve.
Holistic mushonga wekurapa zano rekenza yekenza yepamusoro
1. Mutsara wekutanga kurapwa
Sarudzo dzekurapa kweyepamusoro colorectal cancer dzinosanganisira chemotherapy, yakanangwa uye immunotherapy. Pamberi pekurapa, kuongororwa kwemajini kunofanira kuitwa, nokuti chiremba achaita chirongwa chekurapa zvichienderana nenzvimbo yechirwere chepakutanga, kuchinja kwemajini uye kuongorora biomarker.
Iyo kemesitiri yekenza yakajeka kenza inowanzo sarudza yakawanda-mishonga musanganiswa. Vanachiremba vanobatana uye vanowirirana zvichienderana nemamiriro chaiwo emurwere. Iyo inowanzo shandiswa yekutanga standard mubatanidzwa scheme ndeinotevera:
1. FOLFOX (LV / 5-fluorouracil + oxaliplatin)
2. CAPEOX (Xeloda (Capecitabine) + Oxaliplatin)
3. FOLFIRI (LV / 5-fluorouracil + irinotecan)
4. FOLFOXIRI (LV / 5-fluorouracil + irinotecan + oxaliplatin)
Aya marapirwo anowanzo shandiswa pamwe chete neAvastin® (bevacizumab) kusimudzira kupona, kunyanya pakurapa gomarara rekoroni rekweseri.
Tichitaura nezvazvo, isu tinodawo kuyeuchidza munhu wese kuti chirongwa chekurapa uye kufungidzira kwecolorectal cancer tumors kunoitika kuruboshwe (ichidzika colon, sigmoid colon, rectum) uye kurudyi (kukwira colon, transverse colon, cecum) zvakasiyana zvachose uye haifanirwe kuvhiringidzika. Mushure mekuongororwa, munhu wese anofanirwa kuwana nyanzvi yekuremekedza kuronga chirongwa chekurapa.
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-
Iyo chaiyo hurongwa hwehafu chaiyo yeRAS / RAF yemusango-mhando varwere zvinotevera. Chikamu chakakurudzirwa ini chandinoronga (ndakasarudza): FOLFOX / CapeOx / FOLFIRI ± bevacizumab; FOLFOXIRI ± bevacizumab. Zvichienzaniswa neFOLFIRI + Avastin, FOLFOXIRI + Avastin's mashanu-gore rekupona huwandu hwekupona inofungidzirwa kuti yakapetwa kaviri. Kirasi II yakakurudzira regimen: FOLFOX / FOLFIRI ± cetuximab.
2. Yechipiri-mutsara kurapwa
Mutsara wekutanga, isu tinoshandisa bevacizumab inosanganiswa nekemotherapy. Kana kurapwa kusiri kushanda, tinogona kuchinja chemotherapy regimen uye kuramba tichishandisa bevacizumab. Ehezve, zvakare zvinokwanisika kushandura imwe yakanangwa mushonga panguva imwechete seye chemotherapy regimen, kushandukira kuabercept, kana ramucirumab.
3. Yechitatu-mutsetse uye kumashure-mutsara kurapwa
Sarudzo yemutsara wekutanga uye yechipiri-mutsara wemishonga sarudzo yegomarara remukati kazhinji mamwe akajairwa chemotherapy mishonga nemishonga inonangwa. Kutanga kubva pamutsetse wechitatu kurapwa ndeyekumashure kurapwa. Chirongwa chekurapa chemashure chinogona kushandisa mimwe mishonga yemuromo chemotherapeutic ichangobva kubuda, kusanganisira TAS-102, pamwe neS-1 (tegio), rifafine, kana imwe immunotherapy, yakadai sepembrolizumab (MSI-H).
Kufambira mberi mune chaiyo yakanangwa kurapwa kwecolorectal cancer
Mune iyo 2017 vhezheni yecolorectal cancer yekurapa nhungamiro, zvinokurudzirwa zvekuongorora majini zvinongosanganisira KRAS, NRAS, dMMR uye MSI-H, uye mune yazvino yekurapa nhungamiro muna 2020, zvinangwa zvitsva seBRAF, HER2, NTRK, nezvimwewo ichangobatanidzwa Point, kuburikidza nemajini ekuyedza, kuti tinzwisise mamwe mamorekuru ruzivo rwecolorectal cancer, inogona kutibatsira kuwana mimwe mishonga sarudzo. Ivhareji yekupona kwevarwere inopfuura makore matatu, inova budiriro huru inounzwa nemushonga chaiwo.
1. Ndeapi majini anofanirwa kuongororwa varwere vegomarara
Mushure mekuongororwa, chiremba anofanira kuitisa kuongororwa kwemageneti emurwere wega wega aine metastatic colorectal cancer (mCRC) nekukurumidza sezvinobvira kuti aone chikamu chechirwere ichi, nekuti ruzivo urwu rwunofanotaura kufungidzira kwekurapwa, senge HER2 amplification inoratidza anti-EGFR kurapwa Kurwisa zvinodhaka. Aya majeni anotevera anofanira kuongororwa!
MSI, BRAF, KRAS, NRAS, RAS, HER2, NTRK.
2. Zvinangwa uye zvinodhaka zvakanangwa izvo zvinogona kurapwa izvozvi
VEGF: Bevacizumab, Apsip
VEGFR: ramucirumab, rigofinib, fruquintinib
EGFR: cetuximab, panitumumab
PD-1 / PDL-1: pamluzumab, nivolumab
CTLA-4: Ipilimumab
BRAF: Vimofinil, Connefini
NTRK: Larotinib
Rondedzero yezvakananga uye immunotherapy zvinodhaka zvecolorectal cancer yakagamuchirwa kusvika zvino kumba nekune dzimwe nyika:
| R & D kambani | Chinodhaka chinodhaka | Zita remushonga wakananga | Nguva yekutengesa | Is China mumugwagwa |
| Bristol-Myers Squibb | Her1 (EGFR / ErbB1) | Cetuximab (cetuximab) | 2006 | Ehe |
| Takeda / Amgen | Her1 (EGFR / ErbB1) | Panitumumab (panitumumab) | 2005 | kwete |
| Bayer | KIT / PDGFRβ / RAF / RET / VEGFR1 / 2/3 | regorafenib (regofenib) | 2012 | Ehe |
| Hutchison whampoa | VEGFR1 / 2/3 | Fruquintinib (fruquintinib) | 2018 | Ehe |
| Sanofi | VEGFR A / B | Ziv-aflibercept (Abercept) | 2012 | kwete |
| Eli Lilly | VEGFR2 | Ramucirumab (ramucirumab) | 2014 | kwete |
| Genentech | VEGFR | Bevacizumab (bevacizumab) | 2004 | Ehe |
| Bristol-Myers Squibb | PD-1 | Nivolumab (Nivolumab) | 2015 | Ehe |
| Pfizer | HURI V600E | Encorafenib (Connefini) | 2020 | kwete |
| Bristol-Myers Squibb | CTLA-4 | Ipilimumab (Ipilimumab) | 2011 | kwete |
Zviratidzo zvecolorectal cancer yakanangwa zvinodhaka
Zviratidzo zvebevacizumab zviri : metastatic colorectal cancer and advanced, metastatic or recurrent isina-diki kenza yemapapu kenza.
Zviratidzo zve trastuzumab zviri : HER2-positive metastatic breast cancer, HER2-positive early breast cancer, HER2-positive metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma patients.
Zviratidzo zvePertuzumab zviri : This product is suitable for combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with high-risk recurrence of HER2-positive early kenza yebonde.
Zviratidzo zveNivolumab ndizvo : epidermal growth factor receptor (EGFR) gene mutation negative and anaplastic 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).
Zviratidzo zve regorafenib zviri : varwere vakamborapwa metastatic colorectal cancer. Durvalumab, Tremelimumab, Ipilimumab, uye lapatini
b haisati yavapo kuChina.
EGFR geni shanduko
Epidermal growth factor receptor (EGFR) inoitika munenge gumi muzana yekenza yekenza, kazhinji kuruboshwe.
Cetuximab uye panitumumab zvakagamuchirwa zviri pamutemo neDFA muna2004 na2006 yekurapa kenza yemhando yepamusoro.
Zita remishonga: panitumumab (Vectibix)
Chinangwa: EGFR
Mugadziri: Amgen (kunze)
Zviratidzo: EGFR yakanaka kenza yakajeka kenza, KRAS isina kunaka colorectal cancer
Zita remishonga: Cetuximab (Erbitux)
Chinangwa: EGFR
Mugadziri: Merck (kunze)
Indications: advanced colorectal cancer, kenza yemusoro neyemutsipa
BRAF V600E geni shanduko
7-10% yevarwere vecancer cancer vanotakura BRAF V600E mutation. Iyo BRAF V600E shanduko ndeye BRAF inomutsa shanduko uye ndiyo musiyano neiyo yakanyanya chikamu cheBRAF.
Iine yakasarudzika makiriniki maitiro:
Inonyanya kuoneka mukoloni yekurudyi;
Chiyero cheDMMR chakakwirira, chinosvika 20%;
Kufungidzira kwakashata kwe BRAF V600E shanduko;
Atypical kuchinjisa modhi;
Varwere vane BRAF mutant genes vanowanzove nehurombo kufungidzira, uye mimwe mitsva chaiyo inorwisa kenza mishonga yakaratidzirwa kuti yakapetwa kaviri nguva yekupona.
Chidzidzo chacho chakawana kuti FOLFOXIRI + bevacizumab inogona kunge iri yekurapa kwakanyanya kune varwere vane BRAF shanduko.
Iwo NCCN nhungamiro yeiyo vhezheni V2 2019 inokurudzira wechipiri-mutsara kurapwa kwemasastatic colorectal kenza yeBRAF 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 Braftovi second drug regimen the first targeted therapy approved by the FDA for patients with mCRC carrying BRAF mutations.
Kras gene shanduko
KRAS yemusango-mhando kenza yekoloni ndiyo yekutanga-kurapa kurapwa kwesarudzo kune yakanangwa yekubatanidza chemotherapy, saka ndeipi mhando yekemotherapy sarudzo yekusarudza?
Paunenge uchisarudza chimwe chakanangwa chinodhaka, zvinokurudzirwa kusarudza chemotherapy regimen ine OS yakareba, ndokuti, cetuximab inofanira kusanganiswa neFOLFOX, uye bevacizumab inofanira kusanganiswa neFOLFIRI. Sarudzo yakasarudzika yehurongwa inoda kusanganiswa nekiriniki yakatarwa kuongororwa:
Kana paine tariro yekurapa, cetuximab inosanganisirwa nekemotherapy inowanzodiwa, nekuti ichangoburwa chinangwa checetuximab chakakwirira kupfuura bevacizumab;
Kune varwere vane chirwere chemberi chisingarapike, bevacizumab inosanganiswa nekemotherapy inogona kushandiswa seyekutanga mutsara, ichiteverwa necetuximab kana panitumumab.
Varwere vane metastatic colon cancer vanofanirwa kuyerwa neRAS mutation chinzvimbo kusanganisira KRAS neNRAS. Zvirinani chimiro cheKRAS exon 2 chinofanira kutemerwa.
Kana mamiriro ezvinhu achibvumidza, KRAS exon 2 exon uye NRAS mamiriro ekuchinja anoda kujekeswa.
Bevacizumab yakasanganiswa neaviri-zvinodhaka chemotherapy inogona kuunza PFS (yepakati kufambira mberi-isina kupona) uye OS (kupona kwese) mabhenefiti kune varwere vane KRAS shanduko.
Kune varwere vane RAS shanduko, kushandiswa kwecetuximab kunogona kukanganisa maitiro ese ehutano.
Varwere vane KRAS shanduko kana NRAS shanduko havafanire kushandisa cetuximab kana panitumumab.
HER2 kukwidziridzwa
HER2 kukurudzira kana kuwedzera kufungidzira kwakawanikwa mu2% kusvika 6% yevarwere vane cancer yepamusoro kana metastatic colorectal.
Pertuzumab and trastuzumab combine with different HER2 domains to produce synergistic inhibition on tumarara masero.
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 yakanangwa kurapwa may benefit patients.
NTRK gene fusion shanduko
Vanenge 1 kusvika ku5% yevarwere vegomarara rekoloni vanokudziridza kusanganiswa kweNTRK, uye kuyerwa kweNNG kunokurudzirwa
From January 23 to January 25, 2020, the American Society of Clinical Oncology Gastrointestinal Tumor Symposium (ASCO-GI) specifically analyzed the clinical drug effects of patients with gastrointestinal tumors carrying NTRK fusion protein.
Mhedzisiro yekubvunzurudza yakaratidza kuti huwandu hwekuregererwa kweiyo gastrointestinal cancer subgroup yaive 43%, uye huwandu hwekuregererwa kwevarwere vegomarara rekoloni yaive 50%. Nguva yekupindura inosiyana zvakanyanya, kubva pamwedzi 3.5 kusvika pamwedzi inopfuura 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.
Mukadzi ane makore makumi manomwe nemashanu ane metastatic colorectal cancer (CRC) ane rombo rakanaka:
Primary colon tumarara.
Kenza yePeritoneal.
Chiropa metastasis.
Entratinib 1600mg / m 2 yakatorwa nemuromo kamwe chete pasvondo kamwe pavhiki kwemazuva mana akateedzana (kureva mazuva mana / mazuva matatu abviswa), mazuva ese makumi maviri nemasere kwemavhiki matatu akateedzana. Mushure memavhiki masere ekurapwa, ronda racho rakadzikira zvakanyanya.
Colorectal cancer cancerotherapy uye nyowani nyowani yekugadzira
Kufungidzira kurongeka: MSI-H uye BRAF yemhando yemhando> MSI-H uye BRAF mutant> MSS uye BRAF yemhando yemhando> MSS neBRAF mutant.
1. MSI-H / dMMR metastatic colorectal cancer
Yakakwira microsatellite kusagadzikana (MSI-H) yakanaka yekufungidzira chinhu, uye chiyero cheBRAF mutation muMSI-H colorectal cancer inenge 50%.
Immune checkpoint inhibitors mushonga unoshanda weMSI-H. Iyo immune checkpoint inhibitors parizvino inoshanda kune varwere vane MSI-H mhando mCRC inosanganisira pembrolizumab, nivolumab, uye ipilimumab.
Nivolumab / Ipilimumab mubatanidzwa unoratidzira hwakasimba chiitiko mune yekutanga-mutsara kurapwa
Iko kumberi-mutsara musanganiswa weNivolumab (Opdivo) uye ipilimumab (Yervoy) yakaratidza yakasimba uye inogara-kwenguva refu kiriniki kubatsirwa kune varwere vane metastatic colorectal cancer (mCRC), uye bundu rayo iri microsatellite kusagadzikana (MSI-H) / mismatch repair Chikanganiso (dMMR) -a FACP Heinz-Josef Lenz, MD, vakati vanhu vane hunyanzvi hwekufungidzira nhoroondo.
MuChikamu II ChekuongororaMate-142 kuyedza, ivo vaongorori vakaongorora kuchengetedzeka uye kushanda kweiyo nivolumab pamwe neyepasi-dhamu ipilimumab sekutanga-mutsara kurapwa kwevarwere vane MSI-H / dMMR mCRC (n = 45). Mhedzisiro yapfuura yakatumirwa kumusangano we2018 ESMO wakaratidza kuti huwandu hwekupindura (ORR) hwevarwere makumi mana nevashanu hwaive 45%, uye chirwere chekudzivirira chirwere chaive 60%. Pamusangano wegore negore we84 ASCO, kiriniki yekuvandudza kwekutongwa yakaziviswa Panguva yekutevera yepakati pemwedzi 2019, chiyero cheORR kumubatanidzwa chakaongororwa nemuferefiti chakawedzera kusvika pa19.9%, uye 64% yevarwere vaive nehutachiona hwehutachiona kwemasvondo-84.
2. MSS kenza yakajeka
Kubudirira kutsva muMSS yakajeka kenza: regorafen
ib (Stivarga) + nivolumab
Kumurwere ane chirwere chemicrosatellite stabilization (MSS), vangangoita makumi mashanu nematatu varwere vakagamuchira [mubatanidzwa werapi] uye vakawana huwandu hwekupindura hwe53%, izvo zvisina kuzikanwa mune ino chikamu chevarwere vanokanganisa.
Pane zvinoramba zvichitaurwa zvinoratidza kuti anti-VEGF therapy inogona kuve nehukama hwekuita ne PD-1 blockade. Zvino, ino inguva yekutanga pakati pehuwandu hweMSS. Nokubatanidza nzira mbiri dzekurapa idzi, takaona mhedzisiro inoshamisa. Naizvozvo, nekubatanidza nzira dzekurwisa-VEGF nekudzvinyirira immune kudzvinyirira, varwere vane chirwere cheMSS vanozove nekurarama kwakakura.
Chinyorwa kupedzisa
Munguva yekurapa kwakanangwa, murwere wese ane gomarara rakasarudzika anofanira kupfuura kuona kweMSI, kuongororwa kweRAS neBRAF, uye kuita HER2 kukwidziridzwa, NTRK uye kumwe kuongorora kwejeneti sezvinobvira. Kuongorora maGenetic (NGS) kunozosanganisirwa mune hombe Iyo yekutanga bvunzo yevarwere vazhinji. Iye zvino varwere vekumba vanogona kuyedzwa kuburikidza neGlobal Oncologist Network.
Isu tinorarama mukuchinja kwema molecular kwecolorectal cancer kurapwa. Isu takadzidza zvakawanda nezve mamorekuru genetics yekenza yekoloni uye nemashanduriro azvinoita mumakiriniki ekurapa zvisarudzo. Kuchave nezvakawanda mune ramangwana. Kana zviri zvekufambira mberi kwekutsvagisa uye chirongwa chakanakisa chekurapa checolorectal cancer, chete vepamusoro gomarara nyanzvi kumba nekune dzimwe nyika vane hupfumi hwekiriniki ruzivo. Colorectal kenza varwere vanogona kunyorera kubvunzana nevane masimba masimba kuburikidza neGlobal Oncologist Network kuti vawane yakanyanya kurapa chirongwa.
