Pangobatan kanker kolorektal 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 kanker titik 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 kangker colorectal has increased from less than one year to 3 years, and 20% of patients can survive for 5 years or longer.

Dina taun 2020, naon pilihan pangobatan anyar anu sayogi pikeun penderita kanker koloréktal? Naon ubar anyar anu badé dipasar, Departemen Médis Jaringan Onkologi Global parantos nyusun inpormasi pangénggalna pikeun rujukan anjeun.

Strategi pangobatan ubar holistik pikeun kanker usus besar

1. Perlakuan garis kahiji

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.

Kimia kanker kolorékal biasana milih kombinasi multi-ubar. Dokter ngagabungkeun sareng cocog sareng kaayaan pasien anu saleresna. Skéma kombinasi standar awal anu biasa dianggo sapertos kieu:

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

2. CAPEOX (Xeloda (Capecitabine) + Oxaliplatin)

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

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

Perlakuan ieu biasana dianggo dina kombinasi sareng Avastin® (bevacizumab) pikeun ningkatkeun kasalametan, utamina pikeun pangubaran kanker usus besar.

Nyarioskeun éta, urang ogé kedah ngingetkeun sadayana yén rencana perawatan sareng prognosis tumor kanker kolorektal anu aya di sisi kénca (titik turun, titik sigmoid, réktum) sareng sisi katuhu (titik naek, titik transversal, cecum) béda-béda. jeung teu matak bingung. Saatos diagnosis, sadayana kedah milarian ahli anu otoritatif pikeun nyusun rencana perawatan.

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-

Rencana khusus pikeun satengah katuhu RAS / RAF penderita jenis liar nyaéta kieu. Tingkat anu disarankeun ku kuring direncanakeun (pikaresep): FOLFOX / CapeOx / FOLFIRI ± bevacizumab; FOLFOXIRI ± bevacizumab. Dibandingkeun sareng FOLFIRI + Avastin, FOLFOXIRI + Avastin's 5-taun tingkat salamet salamet diperkirakeun dua kali. Kelas II dianjurkeun regimen: FOLFOX / FOLFIRI ± cetuximab.

2. Perawatan garis kadua

Dina garis kahiji, urang bakal nganggo bevacizumab digabungkeun sareng kémoterapi. Upami pangobatanna henteu épéktip, urang tiasa ngarobih rézim kémoterapi sareng teras nganggo bevacizumab. Tangtosna, ogé dimungkinkeun pikeun ngarobih ubar anu dituju anu sami dina waktos anu sami sareng rézim kémoterapi, janten robih kana abercept, atanapi ramucirumab.

3. Perlakuan garis katilu sareng garis tukang

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).

Kamajuan dina terapi sasaran anu pas pikeun kanker koloréktal

Dina versi 2017 tina pedoman pangobatan kanker koloréktal, rekomendasi pikeun tés genetik ngan ukur ngalibetkeun KRAS, NRAS, dMMR sareng MSI-H, sareng dina panduan pangubaran anu paling anyar dina taun 2020, targét énggal sapertos BRAF, HER2, NTRK, jst. karek kalebet Point, ngalangkungan uji coba genetik, pikeun ngartos langkung seueur inpormasi molekular kanker koloréktal, tiasa ngabantosan kami mendakan langkung seueur pilihan pangobatan. Rata-rata tingkat salamet pasién langkung ti 3 taun, nyaéta kamajuan anu ageung dibawa ku ubar presisi.

1. Gén anu mana anu kedah diuji pikeun penderita kanker koloréktal

Saatos diagnosis, dokter kedah ngalaksanakeun tés genetik unggal pasién sareng kanker kolorektal metastatik (mCRC) gancang-gancang pikeun nangtoskeun kelompok kelompok panyawat, kusabab inpormasi ieu tiasa ngaduga ramalan pangobatan, sapertos amplifikasi HER2 nunjukkeun anti-EGFR Perlakuan tahan Narkoba. Gén ieu kedah diuji!

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

2. Target sareng ubar target anu ayeuna tiasa diubaran

VEGF: Bevacizumab, Apsip

VEGFR: ramucirumab, rigofinib, fruquintinib

EGFR: cetuximab, panitumumab

PD-1 / PDL-1: pamluzumab, nivolumab

CTLA-4: Ipilimumab

BRAF: Vimofinil, Connefini

NTRK: Larotinib

Daptar ubar target sareng imunoterapi kanggo kanker koloréktal anu parantos disahkeun dugi di bumi sareng di mancanagara:

Indikasi pikeun ubar target kanker koloréktal

Indikasi bevacizumab nyaéta : metastatic colorectal cancer and advanced, metastatic or recurrent kanker paru sél non-leutik.

Indikasi pikeun trastuzumab nyaéta : HER2-positive metastatic breast cancer, HER2-positive early breast cancer, HER2-positive metastatic gastric adénokarsinoma or gastroesophageal junction adenocarcinoma patients.

Indikasi pikeun Pertuzumab nyaéta : This product is suitable for combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with high-risk recurrence of HER2-positive early kanker payudara.

Indikasi Nivolumab nyaéta : 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).

Indikasi regorafenib nyaéta : patients with previously treated metastatic colorectal cancer. Durvalumab, Tremelimumab, Ipilimumab, and lapatini
b henteu sayogi di Cina.

Mutasi gén EGFR

Reséptor faktor pertumbuhan Epidermal (EGFR) lumangsung dina sakitar 10% kanker titik, paling umum di kénca.

Cetuximab sareng panitumumab resmi disahkeun ku FDA dina 2004 sareng 2006 pikeun pangobatan kanker koloréktis anu maju.

Nami ubar: panitumumab (Vectibix)

Sasaran: EGFR

Pabrikan: Amgen (luar)

Indikasi: EGFR kanker kolorektal positip, kanker kolorektal KRAS négatip

Nami ubar: Cetuximab (Erbitux)

Sasaran: EGFR

Pabrikan: Merck (luar)

Indications: advanced colorectal cancer, kanker sirah sareng beuheung

Mutasi gén BRAF V600E

7-10% pasien kanker usus besar ngagaduhan mutasi BRAF V600E. Mutasi BRAF V600E mangrupikeun mutasi BRAF anu ngaktipkeun sareng mangrupikeun varian kalayan proporsi paling tinggi tina BRAF.

Boga ciri klinis anu unik:

Utamana némbongan dina titik katuhu;

Proporsi dMMR luhur, ngahontal 20%;

Ramalan goréng tina mutasi BRAF V600E;

Modeu transfer atipikal;

Pasien sareng gén mutan BRAF biasana ngagaduhan ramalan anu goréng, sareng sababaraha ubar anti kanker anu pas parantos kabuktosan waktos hirup dua kali.

Panilitian mendakan yén FOLFOXIRI + bevacizumab tiasa janten pangobatan anu pangsaéna pikeun pasién anu mutasi BRAF.

Pitunjuk NCCN pikeun vérsi V2 2019 nyarankeun perlakuan kadua pikeun kanker kolorektal metastatik pikeun 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 Braftovi second drug regimen the first targeted therapy approved by the FDA for patients with mCRC carrying BRAF mutations.

Mutasi gén Kras

Kanker kolon tipe liar KRAS mangrupikeun pangobatan pilihan kahiji pikeun kémoterapi kombinasi anu ditujukeun, janten naon jinis pilihan kémoterapi kanggo dipilih?

Nalika milih ubar anu ditujukeun, disarankeun milih rézim kémoterapi sareng OS anu langkung lami, nyaéta cetuximab kedah digabungkeun sareng FOLFOX, sareng bevacizumab kedah digabungkeun sareng FOLFIRI. Pilihan khusus rencana kedah digabungkeun sareng analisis spésipik klinis:

Upami aya harepan pikeun tamba, cetuximab digabungkeun sareng kémoterapi umumna langkung dipikaresep, kusabab efisiensi tujuan cetuximab anu anyar langkung luhur tibatan bevacizumab;

Pikeun pasién anu kaserang panyawat anu teu tiasa diubaran, bevacizumab digabungkeun sareng kémoterapi tiasa dianggo salaku garis anu munggaran, dituturkeun ku cetuximab atanapi panitumumab.

Penderita kanker usus besar metastatik kedah diuji pikeun status mutasi RAS kalebet KRAS sareng NRAS. Sahenteuna status KRAS exon 2 kedah ditangtoskeun.

Upami kaayaan ngamungkinkeun, KRAS exon 2 exon sareng status mutasi NRAS kedah diklarifikasi.

Bevacizumab digabungkeun jeung kémoterapi dua-ubar bisa mawa PFS (median progression bébas survival) jeung OS (sakabeh survival) mangpaat pikeun penderita mutasi KRAS.

Pikeun pasién anu mutasi RAS, panggunaan cetuximab tiasa mangaruhan pangaruh négatip dina kamampuan sacara umum.

Pasén anu mutasi KRAS atanapi mutasi NRAS kedah henteu nganggo cetuximab atanapi panitumumab.

Amplifikasi HER2

Penguatan HER2 atanapi overexpression dipendakan dina 2% dugi ka 6% pasien kalayan kanker koloréktal maju atanapi metastatik.

Pertuzumab and trastuzumab combine with different HER2 domains to produce synergistic inhibition on tumor sél.

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 Terapi sasaran may benefit patients.

Mutasi fusi gén NTRK

Sakitar 1 dugi ka 5% pasién kanker usus besar nambihan fusi NTRK, sareng dianjurkeun tés NGS.

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

Hasil tés nunjukkeun yén tingkat ré remisi umum tina subgroup kanker gastrointestinal nyaéta 43%, sareng tingkat remisi sakabéh pasien kanker titik nyaéta 50%. Durasi réspon bénten-bénten pisan, ti 3.5 bulan dugi ka langkung ti 14.7 sasih.

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.

Awéwé yuswa 75 taun kangker kanker kolorektal metastatik (CRC) untung pisan:

Tumor kolon primér.

Kanker peritoneal.

Métastasis ati.

Entratinib 1600mg / m 2 dicandak sacara lisan saminggu sakali saminggu sakali salami 4 dinten berturut (nyaéta 4 dinten / 3 dinten cuti), unggal 28 dinten salami tilu minggu berturut. Saatos dalapan minggu pangobatan, lesion dikirangan signifikan.

Imunoterapi kanker koloréktal sareng inventaris terobosan anyar

Urutan prognostik: MSI-H sareng tipe liar BRAF> MSI-H sareng BRAF mutant> MSS sareng tipe liar BRAF> MSS sareng mutan BRAF.

1. Kanker kolorektal MSI-H / dMMR

Ketidakstabilan microsatelit tinggi (MSI-H) mangrupikeun faktor prognostik anu saé, sareng tingkat mutasi BRAF dina kanker kolorékal MSI-H sakitar 50%.

Inhibitor checkpoint imun mangrupikeun pangobatan anu épéktip pikeun MSI-H. The sambetan checkpoint imun ayeuna lumaku pikeun penderita MSI-H tipe mCRC kalebet pembrolizumab, nivolumab, sareng ipilimumab.

Kombinasi Nivolumab / Ipilimumab nunjukkeun kagiatan anu kuat dina pangobatan lini kahiji

Kombinasi garis payun nivolumab (Opdivo) sareng ipilimumab (Yervoy) parantos nunjukkeun kauntungan klinis anu kuat sareng awét dina penderita kanker kolorektal metastatik (mCRC), sareng tumor na nyaéta ketidakstabilan mikrosatelit (MSI-H) / perbaikan henteu cocog (dMMR) -FACP Heinz-Josef Lenz, MD, saur jalma-jalma anu gaduh riwayat ramalan goréng.

Dina uji coba Phase II CheckMate-142, panaliti nalungtik kasalametan sareng khasiat nivolumab plus ipilimumab dosis rendah salaku perlakuan lini munggaran pikeun penderita MSI-H / dMMR mCRC (n = 45). Hasil sateuacanna dikintunkeun dina konperénsi ESMO 2018 nunjukkeun yén tingkat réspon sacara umum (ORR) 45 pasién nyaéta 60%, sareng tingkat pangendalian panyakit nyaéta 84%. Dina Rapat Tahunan ASCO 2019, pembaruan klinis sidang diumumkeun. Dina waktos tindak lanjut median 19.9 sasih, babandingan ORR kana kombinasi anu ditaksir ku panyidik ​​naék janten 64%, sareng 84% pasién gaduh kontrol panyakit ≥12 minggu.

2. Kanker kolorékal MSS

Terobosan anyar dina kanker kolorektal MSS: regorafen
ib (Stivarga) + nivolumab

Pikeun pasién anu ngagaduhan panyakit stabilisasi mikrosatelit (MSS), sakitar 53 pasién nampi [terapi kombinasi] sareng ngahontal tingkat réspon anu luhur 40%, anu henteu pernah kadéngé dina bagian ieu pasién anu tahan.

Aya data anu pengkuh nunjukkeun yén terapi anti-VEGF tiasa gaduh pangaruh sinergis sareng blokade PD-1. Ayeuna, ieu mangrupikeun kahiji kalina diantara populasi MSS. Ku ngagabungkeun dua stratégi pangobatan ieu, urang parantos ningali hasilna anu berkesan pisan. Ku alatan éta, ku ngagabungkeun strategi anti-VEGF kalayan panekanan tékén imun, penderita panyakit MSS bakal ngagaduhan kauntungan salamet anu langkung ageung.

Kacindekan tulisan

Dina jaman terapi anu ditujukeun, unggal pasién anu ngagaduhan kanker koloréktal kedah lulus tina deteksi MSI, analisis mutasi RAS sareng BRAF, sareng ngalakukeun panguat HER2, NTRK sareng deteksi gén sanés sajauh mungkin. Tés genetik (NGS) bakal dilebetkeun kana standar standar ujian awal pikeun kaseueuran pasien. Ayeuna pasién rumah tangga tiasa diuji ngalangkungan Global Oncologist Network.

Urang hirup dina révolusi molekul pangobatan kanker koloréktal. Kami parantos diajar seueur perkawis genetik molekular kanker usus besar sareng kumaha narjamahkeun kana kaputusan perlakuan klinis. Bakal aya deui pikahareupeun. Sedengkeun pikeun kamajuan panilitian pang anyarna sareng rencana pangobatan pangsaéna pikeun kanker koloréktal, ngan ukur ahli kanker luhur di bumi sareng luar negeri anu gaduh pangalaman klinis anu euyeub. Pasien kanker koloréktal tiasa ngalamar konsultasi sareng ahli berwibawa ngalangkungan Global Oncologist Network pikeun kéngingkeun rencana pangobatan anu pangsaéna.