Numutkeun kana laporan panganyarna ti Pusat Pengendalian sareng Pencegahan Panyakit AS (CDC), insiden ampir sadaya kanker parantos turun dina dua dekade katukang, sedengkeun insiden kanker rahim parantos ningkat. Dokter mimiti merhatoskeun kaayaan ieu sareng ngingetan awéwé pikeun merhatoskeun sababaraha masalah utama panyakit ieu.
According to statistics from the American Cancer Society (ACS), more than 90% of uterine cancers occur in the endometrium, called endometrial cancer. Early endometrial cancer has a good prognosis. According to the US Centers for Disease Control and Prevention, the five-year relative survival rate is estimated to be 80% to 90%. Because kanker rahim can usually be diagnosed early, its most typical symptoms are abnormal bleeding before and after menopause, weight loss and pelvic pain. For advanced metastatic patients, treatment options are very limited.
Recently, the US FDA approved the PD-1 inhibitor Keytruda (pabolizumab) in combination with the oral tyrosine kinase inhibitor Lenvima (Levatinib) to treat patients with specific advanced endometrial cancer. It is worth noting that these patients do not require high microsatellite instability (MSI-H) or mismatch repair defect (dMMR) types. As long as the disease continues to progress after receiving early systemic therapy and cannot receive curative surgery or radiotherapy, this new combination therapy can be accepted.
Kedah disebatkeun yén persetujuan anu dipercepat ieu disatujuan sakaligus di Amérika Serikat, Australia sareng Kanada.
Persetujuan ieu dumasar kana hasil panilitian ngeunaan 94 pasién sareng kanker kanker endometrial, teu saurang ogé anu MSI-H atanapi dMMR. Dina pasién ieu, total tingkat réspon (ORR) nyaéta 38.3%, kalebet 10.6% tingkat réspon lengkep (CR) sareng tingkat réspon parsial 27.7%. 69% (n = 25) pasien ngagaduhan durasi réspon (DOR) ≥ 6 bulan.
"Sahenteuna 75% pasién kanker endometrial sanés jinis MSI-H atanapi dMMR, janten persetujuan ti terapi ieu nyayogikeun pilihan pangobatan énggal sareng ngarep-ngarep kaseueuran penderita kanker endometrial.
Ayeuna, kamajuan panilitian sanés kanker endometrial ogé dikenalkeun sakedap di dieu:
01avelumab (antibodi monoklonal Bavincia) digabungkeun sareng talazoparib (tarazopanib)
Sidang anu dipimpin ku Konstantinopoulos ngagunakeun résistansi pamariksaan imun avelumab dikombinasikeun sareng talazoparib sambetan PARP. (Inhibitor Checkpoint mupus jalan pikeun sistim imun narajang kanker; sambetan PARP ngancurkeun sél kanker ku ngahambat kamampuanna pikeun ngalereskeun DNA rusak.) Dina ékspérimén samemehna, avelumab nyaéta Pasien anu kanker kanker endometrial "henteu stabil" efektif pisan, tapi intina teu aktip dina bentuk panyakit "microsatelit stable" (MSS) anu langkung umum. Sidang bakal ngajajah naha ngagabungkeun avelumab sareng sambetan PARP langkung épéktip pikeun penderita panyakit MSS.
02pembrolizumab (pabolizumab) digabungkeun sareng mirvetuximab
A test combining the checkpoint inhibitor pembrolizumab with mirvetuximab. (Pembrolizumab targets an immune checkpoint protein called PD-1; mirvetuximab adds antibodies to drug molecules targeting key structures in rapidly dividing cancer cells.) The trial, led by Jennifer Veneris, MD, of the Gynecologic Oncology Project, will examine the combination Effectiveness in patients with MSS endometrial cancer.
03abemaciclib + LY3023414 + hormone therapy
Sidang sanés anu dipimpin ku Konstantinopoulos bakal nguji kombinasi ubar target abemaciclib + LY3023414 + terapi hormon. (LY3023414 nargétkeun énzim sél kanker anu disebatkeun PI 3 kinase; abemaciclib ngaganggu tahap kritis siklus sél.) 70% dugi ka 90% kanker endometrial dihakan ku éstrogén sareng mimitina ngaréspon terapi pameungpeuk hormon, tapi pamustunganana kambuh. Ku nambihan abemaciclib sareng LY3023414 (aranjeunna tiasa némpél dua bagéan jalur molekular anu sami) pikeun terapi pameungpeuk hormon, panaliti ngaharepkeun pikeun ngungkulan masalah résistansi ubar.
04AZD1775
A trial led by Joyce Liu, MD, MPH, director of clinical research at the Department of Gynecologic Oncology at Dana-Farber, used AZD1775 for patients with high-grade serous uterine cancer that account for 10-15% of endometrial cancer. Such cancers are aggressive and usually recur after standard treatment. The recently opened trial is based on a study led by Dr. Liu and Ursula Matulonis, director of the Dana-Farber Department of Gynecologic Oncology, showing that AZD1775 is active in a patient model with high-grade serous kanker indung.
05dostarlimab (TSR-042)
Hasil tina percobaan GARNET Fase I / II nembe diterbitkeun, sareng tingkat efektip PD-1 inhibitor dostarlimab (TSR-042) pikeun penderita kanker endometrial kambuh atanapi maju caket 30%.
Salaku tambahan, duanana kelompok henteu stabilitas mikro-satelit (MSI-H) sareng stabilitas mikro-satelit (MSS) anu pengkuh.
Dostarlimab (TSR-042) mangrupikeun antibodi monoklonal anti-PD-1 humanisasi babarengan dikembangkeun ku TESARO sareng AnaptysBio. Éta ngariung kana reséptor PD-1 kalayan afinitas anu luhur, maka ngahalangan pangiketna pikeun ligan PD-L1 sareng PD-L2.
Hasilna nunjukkeun yén tingkat épéktip pikeun sakabéh penduduk nyaéta 29.6%, tingkat épéktip pikeun kelompok pasién MSI-H nyaéta 48.8%, sareng tingkat épéktip dina kohort MSS nyaéta 20.3%. Genep pasién (2 MSI-H sareng 4 MSS) ngagaduhan rémisi lengkep.
Saatos median tindak lanjut tina 10 bulan, 89% pasién nampi pangobatan> 6 bulan, sareng 49% pasién nampi pangobatan salami> 1 taun. Salaku tambahan, 84% pasien anu épéktip dina pangobatan masih nampi perlakuan.
Finally, in 85% of MSI-H responders, the total tumor burden was reduced by ≥50%, and 69% of patients with MSS had a total tumor burden of ≥50%.
Dostarlimab mangrupikeun harepan anu énggal pikeun pangobatan kanker endometrial.
The researchers will start further III studies in the second half of 2019. Dostarlimab and chemotherapy will be combined with first-line treatment of endometrial cancer, and we look forward to obtaining promising results soon!
Unggal sidang alamat kakurangan tina perlakuan standar atanapi masalah anu aya dina uji coba ubar énggal. Salaku conto, dua percobaan anu munggaran ditujukeun pikeun ngungkulan kaayaan miskin ayeuna immunotherapy dina penderita panyakit MSS. Katilu ngajawab masalah résistansi kana terapi hormon, sareng kaopat nargétkeun subtipe khusus kanker endoteli.
Kanggo diajar langkung seueur ngeunaan kamajuan panilitian pang anyarna sareng rencana pangobatan pangsaéna pikeun kanker endometrial, ngan ukur ahli kanker anu paling luhur di bumi sareng di mancanagara anu ngagaduhan pangalaman klinis anu euyeub. Anjeun tiasa ngadaptar konsultasi sareng ahli berwibawa domestik sareng internasional ieu pikeun kéngingkeun diagnosis sareng rencana pangobatan anu pangsaéna.
