TROPION-Breast04: a randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naïve early-stage triple negative or HR-low/HER2− breast cancer

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

Published: Jan. 1, 2025

Background: Despite treatment advances for patients with early-stage triple-negative breast cancer (TNBC) and hormone receptor (HR)-low/human epidermal growth factor 2-negative (HER2−) cancer, treatments that improve clinical outcomes while mitigating toxicity are needed. Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate consisting of humanized IgG1 monoclonal antibody attached via plasma-stable cleavable linker to topoisomerase-I inhibitor payload, has shown efficacy alone or in combination durvalumab, selective, high-affinity anti-programmed cell death ligand 1 antibody, early-phase studies. Objectives: The primary objective TROPION-Breast04 is evaluate the safety neoadjuvant Dato-DXd plus durvalumab followed by adjuvant without chemotherapy versus standard care previously untreated TNBC HR-low/HER2− cancer. Design: This an ongoing, international, phase III, open-label, randomized controlled study. Methods analysis: Approximately 1728 (aged ⩾18 years) will be 1:1 eight cycles (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) (1120 mg IV Q3W) nine pembrolizumab (200 chemotherapy. Dual endpoints pathological complete response blinded central review event-free survival investigator assessment. Secondary include overall (key), distant disease-free survival, patient-reported outcomes, safety. Ethics: study approved independent ethics committees and/or institutional boards at each site. All provide written informed consent. Discussion: potential use findings this trial could lead promising options these patients. Trial registration: ClinicalTrials.gov identifier: NCT06112379.

Language: Английский

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Tailoring chemoimmunotherapy de-escalation in early-stage triple-negative breast cancer

The Lancet Oncology, Journal Year: 2025, Volume and Issue: 26(3), P. 273 - 274

Published: March 1, 2025

Language: Английский

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Antibody-drug conjugates in breast cancer: current evidence and future directions

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 20, 2025

Abstract Antibody-drug conjugates (ADCs) are a rapidly evolving class of antitumor drugs and have already revolutionized the treatment strategy many hematologic solid cancers. So far, trastuzumab emtansine (T-DM1), deruxtecan (T-DXd), sacituzumab govitecan (SG) datopotamab (Dato-DXd) four ADCs that been approved by US food drug administration (FDA) in breast cancer, SKB264 has Chinese national medical products (NMPA). Many for cancer currently being tested late-phase clinical trials, with several encouraging results achieved recently. However, major issues arise during use ADCs, including emergence acquired resistance, occurrence treated-related toxicities, identification biomarkers response resistance. increasingly combination other agents, novel next-generation ADC development is progressing rapidly. A better understanding design will promote treatment. In this review, we aim to provide broad overview recent advances cancer. We also propose notable future directions

Language: Английский

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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

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

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Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(12), P. 3728 - 3736

Published: Sept. 14, 2024

Language: Английский

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Improving primary healthcare with generative AI

Nature Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

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Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting

Urologic Oncology Seminars and Original Investigations, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often multiple options a first salvage therapy. Because treatments both may affect overall survival time, they interact unanticipated ways, there is growing need to determine sequences of therapy that maximize while maintaining quality life. The complexity this problem grows if second must be chosen treatment-resistant or following salvage. On November 9, 2023, think tank was convened during the International Kidney Cancer Symposium (IKCS) North America discuss challenges accounting postprogression when estimating (OS) time based on randomized controlled trial (RCT) data. present manuscript summarizes topics discussed, aim encourage adoption statistical methods account effects obtain scientifically valid OS estimation. We highlight limitations traditional ignoring advantages applying more sophisticated estimation design. These include identifying multistage treatment strategies, correcting confounding due effects, conducting Sequentially Multiple Assignment Randomized Trials (SMARTs) unbiased comparisons between strategies. emphasize critical role patient input design, potential information technology (IT) support complex designs real-time data analyses. By addressing these challenges, future RCTs can better inform clinical decision-making improve outcomes RCC.

Language: Английский

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Moving toward response-adapted trials in oncology

Nature Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Language: Английский

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A roadmap to reduce the incidence and mortality of breast cancer by rethinking our approach to women’s health

Breast Cancer Research and Treatment, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Despite progress, breast cancer remains the most feared disease among women. In USA alone, incidence is now almost 300,000 new cancers per year, a rate that has nearly doubled in last 30 years. Most women survive, but over 40,000 year still die of their National Cancer Institute [Internet]. [cited 2024 Nov 4]. Breast (Female) - Stat Facts. Available from: https://seer.cancer.gov/statfacts/html/breast.html. It diagnosed and second leading cause death. Important disparities exist outcomes African American women, where at higher rates, are younger, more advanced stage. We proposing radical shift our thinking about prevention with an aspiration to dramatically lower incidence. driven by steroid hormones. Throughout life course, offered array hormonal treatments for menstrual cycle control, family planning, vitro fertilization, postpartum weaning, menopausal symptom management. There mixed data on extent which each these may contribute increased or decreased risk cancer. These endocrine manipulations could represent great opportunity potentially reduce improve quality survivors. To date, they have not been designed explicitly risk. A holistic approach will require scientists, drug developers, oncologists, obstetricians, gynecologists, endocrinologists, radiologists, medicine/internists work together toward common goal reducing while addressing other critical issues women's health.

Language: Английский

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Estrogen signaling in early-stage breast Cancer: Impact on neoadjuvant chemotherapy and immunotherapy

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 132, P. 102852 - 102852

Published: Nov. 13, 2024

Neoadjuvant chemoimmunotherapy (NACIT) has been shown to improve pathologic complete response (pCR) rates and survival outcomes in stage II-III triple-negative breast cancer (TNBC). Promising pCR rate improvements have also documented for selected patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) (BC). However, one size does not fit all predicting which will benefit from NACIT remains challenging. Accurate predictions would be useful minimize immune-related toxicity, can severe, irreversible, potentially impact fertility quality of life, identify need alternative treatments. This review aims capitalize on the existing translational clinical evidence predictors treatment early-stage BC treated neoadjuvant chemotherapy (NACT) NACIT. It summarizes suggesting that NACT/NACIT effectiveness may correlate pre-treatment tumor characteristics, including mutational profiles, ER expression signaling, immune cell presence spatial organization, specific gene signatures, levels proliferating versus quiescent cells. predominantly qualitative descriptive nature many studies highlights challenges integrating various potential determinants into a validated, comprehensive, multimodal predictive model. The novel multi-modal approaches, such as those based artificial intelligence, overcome current unclear, these tools are free bias shortcut learning. Despite limitations, rapid evolution technologies, coupled further efforts basic research, holds promise improving outcome early HER2- BC.

Language: Английский

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