دانلود مقاله شاخص های فعلی و دیدگاه های آتی برای داروی آنتی بادی تجویزی
خلاصه
معرفی
فعالیت ADC بر متاستازهای مغزی سرطان پستان: داده های پیش بالینی
فعالیت بالینی ADC تایید شده در حال حاضر بر متاستازهای مغزی سرطان پستان
اثربخشی ساختارهای جدید ADC بر متاستازهای مغزی سرطان پستان
نتیجه گیری و دیدگاه ها
بیانیه مشارکت نویسنده CRediT
اعلامیه منافع رقابتی
قدردانی
منابع
Abstract
Introduction
Activity of ADC on brain metastases of breast cancer: Preclinical data
Clinical activity of currently approved ADC on brain metastases of breast cancer
Efficacy of new ADC constructs on brain metastases of breast cancer
Conclusions and perspectives
CRediT authorship contribution statement
Declaration of Competing Interest
Acknowledgments
References
چکیده
سرطان سینه یکی از علل اصلی متاستازهای مغزی و لپتومننژال است که پیش آگهی آن تا به امروز ضعیف است. اکثر مطالعات بیماران مبتلا به متاستازهای مغزی فعال (BM) و به ویژه مبتلا به متاستازهای لپتومننژیال (LM) را کنار گذاشتند که فقدان نوآوری درمانی در این زمینه را توضیح می‌داد. در حال حاضر، مدیریت استاندارد بیماران مبتلا به BM سرطان سینه بر اساس ترکیبی از جراحی، رادیوتراپی و درمان های سیستمیک است. اخیراً، نسل سوم ترکیبات داروی آنتی بادی (ADCs)، مدیریت سرطان متاستاتیک سینه را متحول کرده است. Trastuzumab deruxtecan و Sacituzumab govitecan در واقع بهبود قابل توجهی در نتایج بقا نشان داده اند و اکنون می توانند در طیف گسترده ای از زیرگروه های سرطان پستان استفاده شوند. با این حال، اطلاعات کمی در مورد اثربخشی ADC های نسل سوم بر BM و LM سرطان پستان در دسترس است. از آنجایی که زمینه ADCs به سرعت در حال تکامل است، با ساختارهای جدیدی که وارد توسعه بالینی دیرینه می شوند، در این بررسی ما اثربخشی کونژوگه های تایید شده و امیدوارکننده جدید را بر روی بیماران مبتلا به BM و LM سرطان پستان توصیف می کنیم.
Abstract
Breast cancer is one of the main cause of cerebral and leptomeningeal metastases, the prognosis of which remains poor to this day. Most studies excluded patients with active brain metastases (BM) and particularly with leptomeningeal metastases (LM) explaining the lack of therapeutic innovation in this area. Currently, the standard management of patients with BM of breast cancer is based on the combination of surgery, radiotherapy and systemic treatments. Recently, third-generation of Antibody-Drug Conjugates (ADCs), have revolutionized the management of metastatic breast cancer. Trastuzumab deruxtecan and Sacituzumab govitecan have indeed shown significant improvements of survival outcomes and can now be used in a wide range of breast cancer subtypes. However, few data are available on the efficacy of third-generation ADCs on BM and LM of breast cancer. As the field of ADCs is rapidly evolving, with new constructs entering the late clinical development, in this review we describe the efficacy of approved and novel promising conjugates on patients with BM and LM of breast cancer.
Introduction
Brain metastases (BM) frequently occur in patients with advanced solid tumors, leading to significant morbidity and mortality. Although the incidence of BM varies across tumor histologies, it is estimated that 10 to 25% of patients with metastatic cancer will develop BM during the course of their disease [1], [2], [3]. Among these tumors, breast cancer (BC) ranks as the second most common cause of BM, following lung cancer. Autopsy studies, considering both symptomatic and asymptomatic lesions, estimate the incidence of BM in BC to be around 20 to 30% [4], [5]. Among metastatic breast cancers (mBC), HER2 positive and triple-negative subtypes are associated with a higher risk of BM (about 30% for each) than luminal subtype (15%) [5].Typically, BM is a late event in the disease course. The median time between the diagnosis of mBC and the onset of BM is approximately 53 months for luminal subtype, 34 months for HER2-positive subtype, and 25 months for triple-negative breast cancer (TNBC) [6]. With the availability of more effective systemic therapies for breast cancer, patients are living longer, resulting in a steady increase in the incidence of BM [7]. Despite therapeutic advancements, patients with BM from BC continue to have a poor prognosis. The median survival varies depending on tumor subtypes, ranging from 7 to 9 months for hormone-receptor positive (HR+)/HER2-negative BC, 16 to 19 months for HR+/HER2-positive BC, 11 to 13 months for hormone-receptor negative (HR-)/HER2-positive BC, and less than 5 months for TNBC [8], [9], [10].
Conclusions and perspectives
In recent years, the advent of novel ADC has significantly transformed the treatment landscape for metastatic breast cancer and holds great promise for improving survival outcomes [62].
However, the management of brain metastases remains a significant challenge. Many studies have either excluded patients with central nervous system involvement or failed to report specific intracranial data when included. Furthermore, there is a paucity of studies specifically investigating the efficacy of third-generation ADC in patients with active brain metastases or leptomeningeal disease.
Nonetheless, the limited available data thus far present promising findings, demonstrating notable activity of ADC in patients with active brain metastases. Given the poor prognosis associated with central nervous system involvement and the effectiveness of ADC, it is imperative to intensify the exploration of these novel treatments in this patient population. Therefore, substantial efforts should be dedicated to designing well-designed clinical trials in this context.