NA.

UNASSIGNED: This review aims to discuss the role and efficacy of Sacituzumab Govitecan in the management of breast cancer.
UNASSIGNED: Breast cancer is the most prevalent type of cancer among women worldwide. This comprehensive review delves into the advancements brought about by Sacituzumab Govitecan in the treatment of metastatic triple-negative breast cancer (TNBC). With a focus on its mode of action, efficacious role, clinical trials, and comparative advantages over conventional chemotherapy, the review highlights the therapy\'s precision in targeting cancer cells through monoclonal antibodies. Sacituzumab Govitecan\'s ability to deliver a chemotherapeutic payload specifically to cancer cells with the Trop-2 receptor sets it apart from traditional chemotherapy, minimizing collateral damage and reducing severe side effects. The impact of Sacituzumab Govitecan on improving progression-free survival, tumor response rates, and, significantly, the quality of life for patients is discussed. This article also sheds light on ongoing trials, FDA recognition, and the therapy\'s potential to transform breast cancer treatment.
UNASSIGNED: In conclusion, Sacituzumab Govitecan shows potential as an innovative therapeutic option for breast cancer, particularly in metastatic breast cancer and triple-negative breast cancer, but it warrants additional research.

UNASSIGNED: The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts.
UNASSIGNED: This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers.
UNASSIGNED: 125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4-11.6) and 11.8 months for SG (95% CI: 8.0-14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8-12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8-6.3) with SG (TNBC 4.9; HR+/HER2-: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1-not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7-not estimable) with SG therapy (TNBC: 12.4, HR+/HER2-: not reached). 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG.
UNASSIGNED: Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.
UNASSIGNED: Trastuzumab-Deruxtecan (T-DXd) und Sacituzumab-Govitecan (SG) sind Antikörper-Wirkstoff-Konjugate (ADCs) der 3. Generation, die vor Kurzem zur Behandlung von metastatischem Brustkrebs über mehrere Subtypen hinweg und in verschiedenen therapeutischen Zusammenhängen zugelassen wurden.
UNASSIGNED: Ziel dieser retrospektiven multizentrischen Studie war es, die Real-World-Daten über die Verträglichkeit, Umsetzbarkeit und Wirksamkeit dieser Wirkstoffe in einer vorbehandelten Real-World-Kohorte in 3 großen deutschen Brustkrebszentren zu bewerten.
UNASSIGNED: Eingeschlossen wurden 125 Patientinnen, die zwischen November 2020 und Juni 2023 mit T-DXd oder SG behandelt wurden (T-DXd: 77 Patientinnen; SG: 48 Patientinnen). Die mediane Behandlungsdauer betrug 6,0 Monate für eine T-DXd- und 3,5 Monate für eine SG-Therapie mit einer medianen Nachbeobachtungszeit von 10,4 Monaten für T-DXd (95%-KI: 8,4–11,6) und 11,8 Monaten für SG (95%-KI: 8,0–14,4). 33,3% der Patientinnen entwickelten eine schwere Neutropenie (CTC ≥ III°) im Verlauf der SG-Therapie, wobei eine numerische Reduktion nach dem primären prophylaktischen Einsatz von G-CSF beobachtet wurde. Bei 8 von 77 Patientinnen (10,4 %) trat eine T-DXd-bedingte Pneumonitis auf. Das mediane progressionsfreie Überleben (mPFÜ) betrug 8,6 Monate (95%-KI: 5,8–12,4) mit T-DXd (HER2+: 10,8; HER2-low: 4,7) und 4,9 Monate (95%-KI: 2,8–6,3) mit SG (TNBC 4,9; HR+/HER2−: nicht erreicht). Das mediane Gesamtüberleben (GÜ) betrug 23,8 Monate (95%-KI: 16,1–nicht schätzbar) mit einer T-DXd-Therapie (HER2+: 27,1; HER2-low: nicht erreicht) und 12,4 Monate (95%-KI: 8,7–nicht schätzbar) mit einer SG-Therapie (TNBC: 12,4, HR+/HER2−: nicht erreicht). Verabreicht wurden 95,7% der im Protokoll vorgegebenen therapeutischen T-DXd-Dosis bzw. 89,6% der vorgegebenen SG-Dosis.
UNASSIGNED: Insgesamt weisen die Daten auf eine gute Umsetzbarkeit, Wirksamkeit und Verträglichkeit von ADC-Therapien in einer realen Umgebung hin.

UNASSIGNED: Initial treatment for hormone-receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC) typically involves endocrine therapy (ET) combined with different targeted agents. When hormonal therapies fail, until recently, the only option available was chemotherapy (ChT), presenting a significant therapeutic challenge. However, the recent introduction of antibody-drug conjugates (ADCs) has provided new treatment alternatives in this context. Sacituzumab govitecan (SG), a novel trophoblast cell-surface antigen 2 (Trop-2)-targeting ADC, has been evaluated following disease progression to ET and ChT in HR+/HER2- ABC.
UNASSIGNED: This review examines the latest clinical trials, including phase I/II and III studies and evaluates the impact of SG on HR+/HER2- ABC. The literature search focused on clinical outcomes, particularly regarding efficacy and safety, comparing them with traditional ChT.
UNASSIGNED: SG has demonstrated to be an effective treatment for patients with HR+/HER2- ABC after progression to ET and cyclin-dependent kinase 4/6 inhibitors (CDKi) in any setting, and at least two ChT-containing regimens in the advanced setting. With a manageable toxicity profile, SG represents a significant advancement in the treatment landscape for this patient population. However, further research is essential to optimize its application and establish long-term benefits.

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate (ADC), was the first ADC approved for patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two prior lines of therapy for advanced disease. Although SG has shown promising clinical activity in treating brain metastases in both ASCENT randomized trials and real-world analysis, its utility in leptomeningeal carcinomatosis (LC) remains underexplored. We report the diagnostic and therapeutic process of a patient who develops extensive LC from TNBC treated with SG. She presented a clinical response after the first cycle of SG with a PFS of 6 months. This case report highlights the need for further inquiry into the use of SG in LC.

BACKGROUND: Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2-negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity.
METHODS: In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68).
RESULTS: We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple-negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression.
CONCLUSIONS: This retrospective, real-world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes.

UNASSIGNED: Treatment of recurrent platinum-resistant high grade serous ovarian cancer (HGSOC) remains a challenge. Novel treatment options for recurrent disease are an unmet need.
UNASSIGNED: A 69-year-old with recurrent, metastatic, platinum-resistant HGSOC overexpressing TROP2 experienced a significant response to the antibody-drug conjugate (ADC) sacituzumab govitecan after multiple failed lines of chemotherapy and targeted treatment. Following sacituzumab govitecan treatment she experienced a confirmed partial response as well as a return of CA-125 to baseline. Having now completed 8 cycles (ie, over 6 months of treatment), her disease continues to demonstrate a response to sacituzumab govitecan treatment. The ADC has been well tolerated at a dose of 10 mg/kg with no dose-limiting toxicity or need for dose reductions.
UNASSIGNED: Sacituzumab govitecan may represent a treatment option for platinum-resistant/recurrent HGSOC that have previously failed prior lines of chemotherapy. Clinical trials with sacituzumab govitecan in platinum-resistant ovarian cancer patients are currently ongoing (https://classic.clinicaltrials.gov/ct2/show/NCT06028932).

BACKGROUND: Antibody drug conjugates represent a promising class of antineoplastic agents comprised of a monoclonal antibody linked to a potent cytotoxic payload for targeted delivery of chemotherapy to tumors. Various antibody drug conjugates have demonstrated impressive efficacy in patients with metastatic urothelial carcinoma in clinical trials, leading to two FDA approved therapies and several other agents and combinations in clinical development.
METHODS: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens.
RESULTS: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable.
CONCLUSIONS: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.

Patients with early-stage triple-negative breast cancer (TNBC) with residual invasive disease after neoadjuvant therapy have a high risk of recurrence even with neoadjuvant and adjuvant treatment with pembrolizumab. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with pre-treated metastatic TNBC. Moreover, preclinical data suggest that topoisomerase I inhibitors may enhance the effects of immune checkpoint inhibitors through activation of the cGAS-STING pathway. Here we describe the international randomized phase III AFT-65/ASCENT-05/OptimICE-RD trial, which evaluates the efficacy and safety of sacituzumab govitecan plus pembrolizumab versus treatment of physician\'s choice (pembrolizumab ± capecitabine) among patients with early-stage TNBC with residual invasive disease after neoadjuvant therapy.Clinical Trial Registration: NCT05633654 (ClinicalTrials.gov)Other Study ID Number(s): Gilead Study ID: GS-US-595-6184Registration date: 1 December 2022Study start date: 12 December 2022Recruitment status: Recruiting.
AFT-65/ASCENT-05/OptimICE-RD is an ongoing clinical trial that is testing a new treatment combination for patients with stage II or III triple-negative breast cancer (TNBC). Stage II–III means the cancer is confined to the breast and/or nearby lymph nodes and can be surgically removed. However, there remains a risk that the cancer could recur after surgery. To reduce this risk, patients with stage II–III TNBC receive anti-cancer medication before and after surgery. For some patients, receipt of anti-cancer medication before surgery produces a pathologic complete response (pCR), meaning there is no observable cancer left behind at surgery. Patients with a pCR have a lower risk of recurrence than patients with residual disease.The AFT-65/ASCENT-05/OptimICE-RD trial includes people with stage II-III TNBC who have residual cancer after completing their course of pre-surgery anti-cancer medication. All participants have any remaining cancer in their breast and/or lymph nodes removed surgically, after which they are randomly assigned to receive one of two treatments. The experimental therapy consists of pembrolizumab along with a medication called sacituzumab govitecan, which kills cancer cells directly and may strengthen the anti-cancer immune response. Pembrolizumab strengthens the anti-cancer immune response, so the hypothesis of this trial is that the two medications will be more effective together. The control therapy consists of pembrolizumab, alone or in combination with a chemotherapy medication called capecitabine, which is the current standard of care. To study the effectiveness of each treatment, the researchers are following up with all participants to learn if and when their breast cancer returns.

This review provides a rationale for using the Food and Drug Administration (FDA)-approved antibody-drug conjugates (ADCs) for implementing as therapy in recurrent refractory germ cell tumors similar to their position in the treatment of other types of chemoresistant solid tumors. Germ cell tumors (GCTs) originate from germ cells; they most frequently develop in ovaries or in the testes, while being the most common type of malignancy in young men. GCTs are very sensitive to cisplatin-based chemotherapy, but therapeutic resistance occurs in a considerable number of cases, which is associated with disease recurrence and poor patient prognosis. ADCs are a novel type of targeted antitumor agents that combine tumor antigen-specific monoclonal antibodies with chemically linked chemotherapeutic drugs (payload) exerting a cytotoxic effect. Several FDA-approved ADCs use as targeting moieties the antigens that are also detected in the GCTs, offering a benefit of this type of targeted therapy even for patients with relapsed/refractory testicular GCTs (rrTGCT) unresponsive to standard chemotherapy.