Targeted Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer: Spotlight on Pembrolizumab DOI Creative Commons
Nusayba A. Bagegni, Andrew A. Davis, Katherine Clifton

et al.

Breast Cancer Targets and Therapy, Journal Year: 2022, Volume and Issue: Volume 14, P. 113 - 123

Published: April 1, 2022

Triple-negative breast cancer (TNBC) is a biologically aggressive yet heterogeneous disease that disproportionately affects younger women and of color compared to other subtypes. The paucity effective targeted therapies the prevalence chemotherapeutic resistance in high-risk, early-stage TNBC pose significant clinical challenges. Deeper insights into genomic immune landscape have revealed key features TNBC, including intrinsic instability, DNA repair deficiency, potentially an immunogenic tumor microenvironment. These advances led landmark trials with checkpoint inhibitors advanced-stage setting, which subsequently translated immunotherapy-based setting recent promising results. Pembrolizumab, anti-programmed death 1 (PD-1) monoclonal antibody, was investigated combination platinum-, taxane- anthracycline-based neoadjuvant chemotherapy followed by adjuvant pembrolizumab monotherapy for patients randomized, double-blind, placebo-controlled phase 3 KEYNOTE-522 trial. In July 2021, US Food Drug Administration (FDA) granted approval based on marked improvement pathologic complete response rate 3-year event-free survival alone. This advance immediately altered longstanding treatment paradigm. Here, we review impact plus discuss immunotherapy-related toxicity considerations, immunomodulatory biomarkers under active investigation, remaining questions future research directions.

Language: Английский

Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations DOI Creative Commons
A. D'Arienzo, Annarita Verrazzo, Martina Pagliuca

et al.

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 62, P. 102113 - 102113

Published: July 27, 2023

Antibody-drug conjugates (ADCs) represent a novel and evolving class of antineoplastic agents, constituted by monoclonal antibody linked to biologically active drugs, delivering cytotoxic compounds at the tumor site, reducing likelihood systemic exposure toxicity. They are generally well tolerated, nevertheless some predictable adverse reactions need careful monitoring timely approach. These include neutropenia, nausea vomiting, alopecia, diarrhea, left ventricular dysfunction, ILD/pneumonitis. The mechanisms leading drug-associated toxicities summarized, prophylaxis protocols appropriate management strategies proposed, based on current literature. This review aims collect most updated evidence potentially occurring during breast cancer treatment with approved or under clinical investigation (advanced stage) ADCs. A focus is dedicated management, aimed preventing and/or promptly address relevant problems, in order avoid premature discontinuation improper dose reduction.

Language: Английский

Citations

47
Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor–Positive Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: Primary Results From TROPION-Breast01 DOI
Aditya Bardia, Komal Jhaveri, Seock‐Ah Im

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ cancer, who had disease progression on endocrine therapy, for whom therapy was unsuitable, and received one to two previous lines setting, were randomly assigned 1:1 Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points progression-free survival (PFS) by blinded independent central review (BICR) overall (OS). RESULTS Patients (n = 365) 367). significantly reduced risk death (PFS BICR hazard ratio [HR], 0.63 [95% CI, 0.52 0.76]; P < .0001). Consistent PFS benefit observed across subgroups. Although OS data not mature, a trend favoring (HR, 0.84 0.62 1.14]). rate grade ≥3 treatment-related adverse events (TRAEs) lower than (20.8% v 44.7%). most common TRAEs (any grade; ≥3) nausea (51.1%; 1.4%) stomatitis (50%; 6.4%) neutropenia (grouped term, 42.5%; 30.8%) ICC. CONCLUSION receiving statistically significant clinically meaningful improvement favorable manageable safety profile, compared Results support as novel treatment option cancer have this setting.

Language: Английский

Citations

16
Trop-2 as a Therapeutic Target in Breast Cancer DOI Open Access
Elizabeth Sakach, Ruth Sacks, Kevin Kalinsky

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5936 - 5936

Published: Nov. 30, 2022

The emergence of Trop-2 as a therapeutic target has given rise to new treatment paradigms for the patients with advanced and metastatic breast cancer. is most highly expressed in triple negative cancer (TNBC), but receptor found across all subtypes. With sacituzumab govitecan, first FDA-approved, inhibitor, providing survival benefit both TNBC hormone positive cancer, additional directed therapies are under investigation. Ongoing studies combination regimens immunotherapy, PARP inhibitors, other targeted agents aim further harness effect inhibition. Current investigations also underway neoadjuvant adjuvant setting evaluate inhibition early stage disease. This review highlights significant impact discovery had on our heavily pretreated whom few options exist, future direction novel therapies.

Language: Английский

Citations

46
The HER2-low revolution in breast oncology: steps forward and emerging challenges DOI Creative Commons
Eleonora Nicolò, Luca Boscolo Bielo, Giuseppe Curigliano

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

Approximately half of breast cancers (BCs), historically categorized as human epidermal growth factor receptor 2 (HER2)-negative, have low expression HER2 defined an immunohistochemical (IHC) score 1+ or 2+ with negative

Language: Английский

Citations

38
How I treat HER2-low advanced breast cancer DOI Open Access
Ilana Schlam, Sara M. Tolaney, Paolo Tarantino

et al.

The Breast, Journal Year: 2023, Volume and Issue: 67, P. 116 - 123

Published: Jan. 12, 2023

Highlights•HER2-low is defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization.•HER2-low not distinct breast cancer subtype, but rather target for potent, novel HER2-directed agents.•Trastuzumab-deruxtecan (TDX-d) approved the treatment pretreated, advanced HER2-low cancer.•Education about risk interstitial lung disease and cardiac toxicity needed prior to initiation TDX-d.AbstractIntroductionTargeting low levels human receptor epidermal growth factor 2 (HER2) has reshaped paradigm half patients with cancer. currently hybridization. Until recently, HER2-targeted agents were ineffective in treating disease.Areas coveredIn this narrative review, we summarize current management We highlight findings DESTINY-Breast 04 phase 3 trial, which confirmed efficacy trastuzumab-deruxtecan (T-DXd) advanced, pretreated also discuss how implement new option algorithms hormone (HR)-positive triple-negative tumors, well optimally manage selected toxicities T-DXd.Expert opinionT-DXd standard care Based on design DESTINY-Breast04 optimal place after first line chemotherapy, both HR-positive Up 10–15% receiving T-DXd are expected develop disease, 1–2% cases can be fatal. Adequate monitoring prompt required minimize impact ILD safely clinical practice.

Language: Английский

Citations

27
Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan DOI Creative Commons
Rebecca S. Heist, Jacob Sands, Aditya Bardia

et al.

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 125, P. 102720 - 102720

Published: March 11, 2024

Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery cytotoxic agents tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising topoisomerase I inhibitor payload monoclonal antibody directed trophoblast cell-surface antigen 2 (TROP2), protein that broadly expressed in several types solid tumors. Dato-DXd being investigated across multiple indications. In ongoing, first-in-human TROPION-PanTumor01 phase study (ClinicalTrials.gov: NCT03401385), encouraging durable antitumor activity manageable safety profile was demonstrated patients advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2– BC), triple-negative (TNBC), non-small cell lung (NSCLC). Improved understanding adverse events (AEs) associated their optimal management essential ensure safe successful administration. Interstitial disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, ocular surface have been identified as AEs special interest (AESIs) for which appropriate prevention, monitoring, essential. This article summarizes incidence AESIs among HR+/HER2 − BC, TNBC, NSCLC reported TROPION-PanTumor01. We report our recommendations AESI prophylaxis, early detection, management, using experience gained from treating occur clinical trials.

Language: Английский

Citations

15
Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial DOI
Rebecca Shatsky, Meghna S. Trivedi, Christina Yau

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(12), P. 3737 - 3747

Published: Sept. 14, 2024

Language: Английский

Citations

11
Emerging Targeted Therapies in Non-Small-Cell Lung Cancer (NSCLC) DOI Open Access

Syeda A. Mina,

Mohamed Shanshal, Konstantinos Leventakos

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 353 - 353

Published: Jan. 22, 2025

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages cancer. Newer advances in common novel oncogenic drivers continue occur at vigorous speed, making it challenging stay up date with rapidly evolving field. In this article, we review emerging perspectives actionable targets We focus on development newer KRAS-directed therapies, particularly non-G12C mutations, pan-RAS inhibitors, RAS-GTP inhibitors. also describe current standard care for EGFR- ALK-altered NSCLC dive into treatments expected be clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, FGFR alterations as Finally, conclude body evidence targeting TROP-2 a target, potentially importance post-targeted therapy scenarios.

Language: Английский

Citations

1
Management of nausea and vomiting induced by antibody–drug conjugates DOI Creative Commons

Jawhara Farhat,

Hitomi Sakai, Junji Tsurutani

et al.

Breast Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

Citations

1
Antibody–Drug Conjugate Revolution in Breast Cancer: The Road Ahead DOI Creative Commons
Thomas Grinda, Elie Rassy, Barbara Pistilli

et al.

Current Treatment Options in Oncology, Journal Year: 2023, Volume and Issue: 24(5), P. 442 - 465

Published: March 25, 2023

Antibody drug-conjugates (ADCs) have revolutionized the treatment of many types cancer, including breast cancer. Recently, two new ADCs been approved, trastuzumab deruxtecan and sacituzumab govitecan; both demonstrated impressive improvements in overall survival, all three subtypes metastatic cancer govitecan luminal triple negative These drugs are results significant progress innovation construction components an ADC, monoclonal antibody, payload, linker, discovery target antigens. ADC engineering has profoundly changed paradigm treatment, on one side being effective tumors considered inherently resistant to payload class other demonstrating activity with very low expression. Yet, it is likely that we just at beginning a era as identification targets introduction constructs combinations will expand field rapidly over coming years.

Language: Английский

Citations

21