AQSh Kasalliklarni nazorat qilish va oldini olish markazlarining (CDC) so'nggi hisobotiga ko'ra, so'nggi yigirma yil ichida deyarli barcha saraton kasalliklari kamaygan, bachadon saratoni bilan kasallanish darajasi esa oshgan. Shifokorlar ushbu holatga e'tibor berishni boshladilar va ayollarga ushbu kasallikning bir nechta asosiy masalalariga e'tibor berishlarini eslatdilar.
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 bachadon saratoni 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.
Eslatib o'tamiz, ushbu tezlashtirilgan tasdiqlash AQSh, Avstraliya va Kanadada bir vaqtning o'zida tasdiqlangan.
Tasdiqlash endometriyal saraton o'smalari bo'lgan 94 bemorni o'rganish natijalariga asoslanadi, ularning hech biri MSI-H yoki dMMR emas. Ushbu bemorlarda umumiy javob darajasi (ORR) 38.3% ni tashkil etdi, shu jumladan 10.6% to'liq javob darajasi (CR) va qisman javob darajasi 27.7%. 69% (n = 25) bemorlarning javob muddati (DOR) ≥ 6 oy bo'lgan.
"Endometrium saratoniga chalingan bemorlarning kamida 75% MSI-H yoki dMMR turiga mansub emas, shuning uchun ushbu terapiyani tasdiqlash endometrium saratoniga chalingan bemorlarning ko'pchiligiga davolashning yangi imkoniyatlarini va umidlarini olib keladi.
Hozirgi vaqtda endometrium saratonining boshqa tadqiqotlari ham bu erda qisqacha tanishtirilgan:
01avelumab (Bavincia monoklonal antikor) talazoparib (tarazopanib) bilan birgalikda
Konstantinopulos boshchiligidagi sinovda immunitet tekshiruvi avelumab inhibitori PARP inhibitori talazoparib bilan birgalikda ishlatilgan. (Tekshirish punkti inhibitörleri immunitet tizimining saraton kasalligiga qarshi kurash yo'lini tozalaydi; PARP inhibitörleri, zararlangan DNKni tiklash qobiliyatiga to'sqinlik qilib, saraton hujayralarini yo'q qiladi.) Oldingi tajribada, avelumab edi "beqaror" endometrium saratoni bilan og'rigan bemorlar juda samarali, ammo aslida kasallikning tez-tez uchraydigan "mikrosatellit barqaror" (MSS) shaklida faol emas. Sinov avelumabni PARP inhibitörleri bilan birlashtirish MSS kasalligi bo'lgan bemorlarda samaraliroq bo'ladimi-yo'qligini o'rganadi.
02pembrolizumab (pabolizumab) mirvetuximab bilan birlashtirilgan
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
Konstantinopulos boshchiligidagi yana bir sinov maqsadli dori abemaciclib + LY3023414 + gormon terapiyasining kombinatsiyasini sinovdan o'tkazadi. (LY3023414, PI 3 kinaz deb nomlangan saraton hujayrasi fermentini maqsad qiladi; abemaciclib hujayra tsiklining muhim bosqichiga xalaqit beradi.) Endometriyal saratonlarning 70% dan 90% gacha bo'lgan qismi estrogen bilan oziqlanadi va dastlab gormonlarni blokirovka qilish terapiyasiga javob beradi, ammo oxir-oqibat relaps. Gormonlarni blokirovka qilish terapiyasi uchun abemaciclib va LY3023414 (ular bir xil molekulyar yo'lning ikki qismiga tegishi mumkin) qo'shib, tadqiqotchilar dori-darmonlarga qarshilik muammosini engishga umid qilmoqdalar.
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 ovaryan saraton.
05dostarlimab (TSR-042)
I/II GARNET sinovining natijalari yaqinda e'lon qilindi va endometrium saratoni qaytalangan yoki rivojlangan bemorlar uchun PD-1 inhibitori dostarlimabning (TSR-042) umumiy samarali darajasi 30% ga yaqin.
Bundan tashqari, mikro-sun'iy yo'ldoshning beqarorligi (MSI-H) ham, mikro-sun'iy yo'ldoshning barqarorligi (MSS) guruhlari ham doimiydir.
Dostarlimab (TSR-042) - bu TESARO va AnaptysBio tomonidan birgalikda ishlab chiqilgan, insonparvarlashtirilgan anti-PD-1 monoklonal antikor. U PD-1 retseptorlari bilan yuqori yaqinlik bilan bog'lanadi va shu bilan PD-L1 va PD-L2 ligandlari bilan bog'lanishini bloklaydi.
Natijalar shuni ko'rsatdiki, butun aholining samarali darajasi 29.6% ni, MSI-H bemorlar guruhining samaradorligi 48.8% ni va MSS kogortasida samarali darajasi 20.3% ni tashkil etdi. Olti bemor (2 MSI-H va 4 MSS) to'liq remissiyaga ega.
10 oylik o'rtacha kuzatuvdan so'ng, bemorlarning 89%> 6 oylik davolanishdi va 49% bemorlar> 1 yil davomida davolanishdi. Bundan tashqari, davolanishda samarali bo'lgan bemorlarning 84% hanuzgacha davolanmoqda.
Finally, in 85% of MSI-H responders, the total shish burden was reduced by ≥50%, and 69% of patients with MSS had a total tumor burden of ≥50%.
Dostarlimab endometrium saratonini davolash uchun yangi umiddir.
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!
Har bir sinov standart davolanishning kamchiliklarini yoki oldingi yangi dori-darmonlarni sinashda topilgan muammolarni hal qiladi. Masalan, dastlabki ikkita sud jarayoni kambag'allarning hozirgi holatini engishga qaratilgan immunoterapiya MSS kasalligi bo'lgan bemorlarda. Uchinchisi gormon terapiyasiga chidamlilik muammosini hal qiladi, to'rtinchisi endotelial saratonning o'ziga xos pastki turlariga qaratilgan.
So'nggi tadqiqot natijalari va endometrium saratoniga qarshi dori-darmonlarning eng yaxshi rejasi haqida ko'proq bilish uchun faqat uyda va chet elda eng yaxshi saraton mutaxassislari boy klinik tajribaga ega. Eng yaxshi tashxis qo'yish va davolash rejasini olish uchun quyidagi mahalliy va xalqaro nufuzli mutaxassislar bilan maslahatlashish uchun murojaat qilishingiz mumkin.
