LBA17 ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC)

Bardia, Aditya; Tolaney, Sara M.; Loirat, Delphine; Punie, Kevin; Oliveira, Mafalda; Rugo, Hope S.; Brufsky, Adam; Kalinsky, Kevin; Cortés, Javier; O’Shaughnessy, Joyce; Dièras, Véronique; Carey, Lisa A.; Gianni, L.; Piccart, Martine; Loibl, Sibylle; Goldenberg, D. M.; Qin, Hong; Olivo, Martin; Itri, Loretta M.; Hurvitz, Sara A.

doi:10.1016/j.annonc.2020.08.2245

Cited by 63 publications

(55 citation statements)

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“…Data from the randomized, phase III, ASCENT trial have been recently presented at 2020 ESMO Congress. SG outperformed standard chemotherapy (capecitabine, eribulin, vinorelbine or gemcitabine as per physician’s choice) in terms of both PFS (median PFS of 5.6 vs 1.7 months) and OS (median OS 12.1 vs 6.7 months), with a safety profile similar to what observed in earlier trials [ 51 ].…”

Section: Established Targets With Approved Adcsmentioning

confidence: 53%

Antibody–drug conjugates in solid tumors: a look into novel targets

2021

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Antibody–drug conjugates (ADCs) are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell killing properties of chemotherapy. They are commonly described as the “Trojan Horses” of therapeutic armamentarium, because of their capability of directly conveying cytotoxic drug (payloads) into the tumor space, thus transforming chemotherapy into a targeted agent. Three novel ADCs have been recently approved, i.e., trastuzumab deruxtecan, sacituzumab govitecan and enfortumab vedotin, respectively, targeting HER2, Trop2 and Nectin4. Thanks to progressive advances in engineering technologies these drugs rely on, the spectrum of diseases sensitive to these drugs as well as their indications are in continuous expansion. Several novel ADCs are under evaluation, exploring new potential targets along with innovative payloads. This review aims at providing a summary of the technology behind these compounds and at presenting the latest ADCs approved in solid tumors, as well as at describing novel targets for ADCs under investigation and new strategies to optimize their efficacy in solid tumors.

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Section: Established Targets With Approved Adcsmentioning

confidence: 53%

Antibody–drug conjugates in solid tumors: a look into novel targets

2021

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“…The ASCENT study [48] was an international, openlabel, randomized phase III trial that evaluated the efficacy of intravenous sacituzumab govitecan (10 mg/kg on days 1 and 8 of a 21-day cycle) versus single-agent TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) in 468 patients with metastatic TNBC who progressed on two or more prior chemotherapies (including a taxane) in the metastatic setting. Of note, patients who progressed within 12 months from the end of (neo)adjuvant therapy were considered as having had a prior line of therapy.…”

Section: Triple-negative Breast Cancermentioning

confidence: 99%

Clinical Development of New Antibody–Drug Conjugates in Breast Cancer: To Infinity and Beyond

Barroso‐Sousa

Tolaney

2021

BioDrugs

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Metastatic breast cancer remains an incurable disease, and new therapies are needed. One major limitation of chemotherapy is the toxicity associated with higher dose exposure. Antibody-drug conjugates (ADCs) are a complex and evolving class of agents specifically designed with the objective of delivering antineoplastic medicines in the most precise and selectively targeted way. ADCs are composed of four key components: (1) the target antigen, (2) an antibody construct, (3) a payload (most commonly a cytotoxic agent), and (4) a linker moiety that couples the payload and the antibody. In this review, we discuss the clinical development of ADCs for the treatment of breast cancer, focusing on two recently FDA-approved agents, trastuzumab deruxtecan and sacituzumab govitecan, and discuss the ongoing efforts exploring new agents. Finally, we summarize the current portfolio of clinical trials that could change the algorithm of treatment for early and advanced breast cancer.

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“…Recently, a phase III study evaluating an antibody-drug conjugate consisting of an anti-Trop2 antibody conjugated with SN-38, the active metabolite of irinotecan, has shown very promising results in metastatic TNBC. 15 Finally, immunotherapy with immune checkpoint inhibitors (anti-programmed cell death protein 1…”

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confidence: 99%

Signaling pathways essential for triple-negative breast cancer stem-like cells

Ehmsen

Ditzel

2020

Stem Cells

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Since the discovery of breast cancer stem cells (CSCs), a significant effort has been made to identify and characterize these cells. It is a generally believe that CSCs play an important role in cancer initiation, therapy resistance, and progression of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor prognosis. Thus, therapies targeting these cells would be a valuable addition to standard treatments that primarily target more differentiated, rapidly dividing TNBC cells. Although several cell surface and intracellular proteins have been described as biomarkers for CSCs, none of these are specific to this population of cells. Recent research is moving toward cellular signaling pathways as targets and biomarkers for CSCs. The WNT pathway, the nuclear factor-kappa B (NF-κB) pathway, and the cholesterol biosynthesis pathway have recently been identified to play a key role in proliferation, survival, and differentiation of CSCs, including those of breast cancer. In this review, we assess recent findings related to these three pathways in breast CSC, with particular focus on TNBC CSCs, and discuss how targeting these pathways, in combination with current standard of care, might prove effective and improve the prognosis of TNBC patients.

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LBA17 ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC)

Abstract: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC)

Cited by 63 publications

References 0 publications

Antibody–drug conjugates in solid tumors: a look into novel targets

Antibody–drug conjugates in solid tumors: a look into novel targets

Clinical Development of New Antibody–Drug Conjugates in Breast Cancer: To Infinity and Beyond

Signaling pathways essential for triple-negative breast cancer stem-like cells

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