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

Post-Progression treatment options after CDK4/6 inhibitors in hormone Receptor-Positive HER2-Negative metastatic breast cancer DOI
Taha Koray Şahin, Alessandro Rizzo, Deniz Can Güven

et al.

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102924 - 102924

Published: March 1, 2025

Language: Английский

Citations

0
Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index DOI Open Access
Jian‐ping Gong, Wenqiu Zhang, Joseph P. Balthasar

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 1032 - 1032

Published: March 20, 2025

Camptothecin and its derivatives (CPTs) are potent antineoplastic agents that exert their effects by inhibiting DNA topoisomerase I, leading to apoptosis during cell proliferation. Since discovery in the 1960s, CPTs have faced challenges such as low water solubility, pH-dependent lactone ring instability, severe off-target toxicities. Despite extensive research, only two CPTs, irinotecan topotecan, received health authority approval. Ongoing clinical trials continue explore use of combination with targeted therapies immunotherapies expand use. Drug delivery systems, including liposomes antibody–drug conjugates (ADCs), significantly enhanced therapeutic index CPTs. Liposomal (Onivyde®, Ipsen, Paris, France) ADCs delivering CPT payloads, trastuzumab deruxtecan (Enhertu®, Daiichi Sankyo, Tokyo, Japan) sacituzumab govitecan (Trodelvy®, Gilead Sciences, Inc., Foster City, CA, USA), demonstrated substantial efficacy safety. There is promise novel strategies inverse targeting co-dosing anti-idiotypic distribution enhancers may utility ADCs. This review highlights discusses approaches further enhance selectivity.

Language: Английский

Citations

0
Toxicities and management strategies of emerging antibody–drug conjugates in breast cancer DOI Creative Commons
Sora Kang, Sung‐Bae Kim

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

Antibody–drug conjugates (ADCs) offer a promising therapeutic approach for various cancers, enhancing the window while mitigating systemic adverse effects on healthy tissues. ADCs have achieved remarkable clinical success, particularly in treating breast cancer, becoming standard therapy across all subtypes, including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative cancer. Although designed to selectively target antigens via monoclonal antibodies, can exhibit toxicity normal tissues, often due off-target of their cytotoxic payloads. Understanding managing these toxicities according established guidelines are crucial ADC efficacy, minimizing events, ultimately improving patient outcomes. This review comprehensively examines employed cancer treatment explores management strategies. Furthermore, we investigate novel beyond trastuzumab deruxtecan sacituzumab govitecan, evaluating potential efficacy corresponding safety profiles.

Language: Английский

Citations

0
TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer DOI Creative Commons
Peter Schmid, Mafalda Oliveira, Joyce O’Shaughnessy

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: April 1, 2025

Background: Standard of care (SoC) for patients with advanced triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score ⩾ 10) is chemotherapy plus anti-PD-(L)1 inhibitors; however, prognosis and survival most poor. Datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate comprising humanized anti-TROP2 IgG1 monoclonal antibody conjugated to potent topoisomerase I inhibitor payload via plasma-stable, cleavable, tetrapeptide-based linker, has shown preliminary activity as mono or combination therapy in advanced/metastatic TNBC. Objectives: TROPION-Breast05 an ongoing randomized, open-label, multicenter phase III study. The primary objective demonstrate the superiority Dato-DXd durvalumab (an anti-PD-L1 antibody) versus SoC treatment PD-L1-high locally recurrent inoperable metastatic Methods design: Patients (⩾18 years) will be randomized 1:1 receive (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) (1120 mg IV Q3W) investigator’s choice (ICC; paclitaxel, nab-paclitaxel, gemcitabine carboplatin) pembrolizumab (200 Q3W). In selected countries, also (1:1:1) third arm monotherapy. study endpoint progression-free (PFS) per blinded independent central review (Dato-DXd vs ICC arm). Overall key secondary endpoint; other endpoints include PFS (investigator-assessed), response rate, duration response, clinical benefit rate at Week 24 (all assessed arm), patient-reported outcomes, safety. Ethics: approved by ethics committees institutional boards each site. All provide written informed consent. Discussion: assess potential role without findings this trial could lead new option these patients. Trial registration: ClinicalTrials.gov identifier: NCT06103864 (Date 27 October 2023).

Language: Английский

Citations

0
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

Citations

18