August 2021: Pembrolizumab (Keytruda, Merck) was approved by the FDA for high-risk, early-stage triple-negative breast cancer (TNBC) as a neoadjuvant treatment in combination with chemotherapy, and later as a single agent as adjuvant treatment following surgery.
Pembrolizumab in conjunction with chemotherapy was also given regular approval by the FDA for patients with locally recurrent unresectable or metastatic TNBC whose tumours express PD-L1 (Combined Positive Score [CPS] 10) as assessed by an FDA-approved test. In November 2020, the FDA gave pembrolizumab expedited approval for this indication.
Neoadjuvant va yordamchi tasdiqlar, shuningdek, tezlashtirilgan tasdiqlash uchun tasdiqlovchi sinov quyidagi sinovga asoslangan edi.
KEYNOTE-522 (NCT03036488) da, randomizatsiyalangan, ko'p markazli, ko'r-ko'rona, platsebo-nazorat ostida o'tkazilgan, yangi tashxis qo'yilmagan yuqori xavfli erta bosqichli TNBC (o'simta kattaligi> 1174 sm, lekin 1 sm) bo'lgan 2 nafar bemor ishtirok etgan. pembrolizumabning yagona agenti sifatida, pembrolizumabning neoadjuvanli kimyoterapiya bilan birgalikda samaradorligi, so'ngra jarrohlik va davom etayotgan bemorlar PD-L1 ifodasidan qat'i nazar, ularning o'smalariga kiritildi.
Pembrolizumab bemorlarga kimyoterapiya yoki platsebo bilan birgalikda 2: 1 nisbatda berildi. Kimyoterapiya protokoli quyida bog'langan dori yorlig'ida batafsil ko'rsatilgan.
Patologik to'liq javob berish darajasi (pCR) va hodisasiz omon qolish samaradorlikning asosiy ko'rsatkichlari (EFS) edi. Kimyoterapiya bilan birgalikda pembrolizumab olgan bemorlarning pCR darajasi 63 % (95 % CI: 59.5, 66.4), faqat kimyoterapiya olgan bemorlarda 56 % (95 % CI: 50.6, 60.6) ga teng edi. EFS epizodi bo'lgan bemorlarning nisbati mos ravishda 123 (16%) va 93 (24%) edi (HR 0.63; 95 foiz CI: 0.48, 0.82; p = 0.00031).
Charchoq/asteniya, ko'ngil aynishi, ich qotishi, diareya, ishtahaning pasayishi, toshma, qusish, yo'tal, nafas qisilishi, pireksiya, alopesiya, periferik neyropatiya, shilliq qavatning yallig'lanishi, stomatit, bosh og'rig'i, vazn yo'qotish, qorin og'rig'i, artralgiya, miyalji va uyqusizlik pembrolizumabni kimyoterapiya bilan birgalikda sinab ko'rgan bemorlarning taxminan 20 foizida tez -tez uchraydigan nojo'ya reaktsiyalar.
Pembrolizumab tomir ichiga 30 daqiqa davomida har uch haftada 200 mg yoki TNBC uchun har olti haftada 400 mg dozada yuboriladi. Neoadjuvanli davolanish uchun pembrolizumab kimyoterapiya bilan birgalikda 24 hafta davomida, so'ngra 27 haftagacha yordamchi davo uchun yagona vosita sifatida beriladi.
