Clinical Guidance on the Monitoring and Management of Trastuzumab Deruxtecan (T-DXd)-Related Adverse Events: Insights from an Asia-Pacific Multidisciplinary Panel DOI Creative Commons

Joanne Chiu,

Soo Chin Lee, Jcm Ho

et al.

Drug Safety, Journal Year: 2023, Volume and Issue: 46(10), P. 927 - 949

Published: Aug. 8, 2023

Trastuzumab deruxtecan (T-DXd)—an antibody–drug conjugate targeting the human epidermal growth factor receptor 2 (HER2)—improved outcomes of patients with HER2-positive and HER2-low metastatic breast cancer. Guidance on monitoring managing T-DXd–related adverse events (AEs) is an emerging unmet need as translating clinical trial experience into real-world practice may be difficult due to practical cultural considerations differences in health care infrastructure. Thus, 13 experts including oncologists, pulmonologists a radiologist from Asia-Pacific region gathered provide recommendations for AE management by using latest evidence DESTINY-Breast trials, our own loco-regional considerations. While subgroup analysis Asian (excluding Japanese) versus overall population DESTINY-Breast03 uncovered no major profile, we concluded that proactive are essential maximising benefits T-DXd. As interstitial lung disease (ILD)/pneumonitis serious AE, should undergo regular computed tomography scans, but frequency have account median time ILD/pneumonitis onset access. appears highly emetic regimen, prophylaxis serotonin antagonists dexamethasone (with or without neurokinin-1 antagonist) considered. Health professionals vigilant treatable causes fatigue, encouraged use support groups low-intensity exercises. To increase treatment acceptance, made aware alopecia risk prior starting Detailed AEs discussed further.

Language: Английский

ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer DOI Creative Commons

P. Tarantino,

Giulia Viale, Michael F. Press

et al.

Annals of Oncology, Journal Year: 2023, Volume and Issue: 34(8), P. 645 - 659

Published: June 1, 2023

Language: Английский

Citations

157
HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis DOI Creative Commons
Ryan Tan, Whee Sze Ong, Kyung-Hun Lee

et al.

BMC Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: March 17, 2022

Abstract Background HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact low expression HER2 on survival outcomes in HER2-negative non-metastatic (BC). Methods Patients with BC from 6 centres within Asian Breast Cancer Cooperative Group (ABCCG) ( n = 28,280) were analysed. was defined as immunohistochemistry (IHC) 1+ or 2+ and situ hybridization non-amplified (ISH−) HER2-zero IHC 0. Relapse-free (RFS) overall (OS) by hormone receptor status 0, ISH− main outcomes. A combined TCGA-BRCA METABRIC cohort 1967) also analysed to explore association between expression, ERBB2 copy number variation (CNV) RFS. Results ABCCG median follow-up 6.6 years; there 12,260 (43.4%) 16,020 (56.6%) BC. The better than (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82–0.93, P < 0.001; OS: HR 0.82, 0.76–0.89, 0.001). On multivariable analysis, prognostic 0.90, 0.85–0.96, 0.002; 0.86, 0.79–0.93, These differences remained significant receptor-positive tumours for OS receptor-negative tumours. Superior observed IHC1+ versus 0.89, 0.83–0.96, 0.85, 0.78–0.93, No seen IHC2+ BCs. In cohorts, CNV independent RFS factor (neutral non-neutral 0.71, 0.59–0.86, 0.001); no mRNA levels found. Conclusions had a superior prognosis compared setting, though absolute modest driven merits further investigation

Language: Английский

Citations

97
Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis DOI Creative Commons
Chiara Molinelli, Flavia Jacobs, Elisa Agostinetto

et al.

ESMO Open, Journal Year: 2023, Volume and Issue: 8(4), P. 101592 - 101592

Published: July 4, 2023

•Patients with HER2-low tumours showed better OS than those HER2-zero cancers in both settings.•No differences were found terms of PFS between patients and tumours.•Patients a lower rate pCR compared to cancers. BackgroundHuman epidermal growth factor receptor 2 (HER2)-low expression breast cancer has been recently identified as new therapeutic target. However, it is unclear if status an independent impact on prognosis.Materials methodsA systematic literature research was carried out identify studies comparing survival outcomes affected by versus cancer. Using random-effects models, pooled hazard ratios (HRs) odds (ORs) 95% confidence intervals (CIs) calculated for progression-free (PFS) overall (OS) the metastatic setting well disease-free (DFS), pathological complete response (pCR) early setting. Subgroup analyses hormone (HoR) out. The study protocol registered PROSPERO (n.CRD42023390777).ResultsAmong 1916 records, 42 including 1 797 175 eligible. In setting, associated significant improved DFS (HR 0.86, CI 0.79-0.92, P < 0.001) 0.90, 0.85-0.95, when status. Improved observed HoR-positive HoR-negative populations, while improvement only subgroup. significantly population (OR 0.74, 0.62-0.88, = subgroup 0.77, 0.65-0.90, 0.001). 0.94, 0.89-0.98, 0.008), regardless HoR No found.ConclusionsCompared status, appears be slightly increased advanced settings, expression. seem rates, especially HoR-positive. Human prognosis. A (n.CRD42023390777). Among found. Compared

Language: Английский

Citations

44
Elacestrant in ER+, HER2– MBC with ESR1-mutated tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy Plus CDK4/6 Inhibitor and in Clinical Subgroups DOI Creative Commons
Aditya Bardia, Javier Cortés, François‐Clément Bidard

et al.

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(19), P. 4299 - 4309

Published: Aug. 1, 2024

Abstract Purpose: Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety versus standard-of-care (SOC) endocrine therapy (ET) in patients estrogen receptor–positive (ER+), HER2− metastatic breast cancer and tumors harboring receptor 1 (ESR1) mutation following ET plus a cyclin-dependent kinase 4/6 inhibitor (ET+CDK4/6i). In ESR1-mutated tumors, we evaluated the efficacy of elacestrant SOC based on prior ET+CDK4/6i duration clinical subgroups ≥12 months. Patients Methods: EMERALD, an open-label phase III trial, randomly assigned ER+, who had received 1–2 lines ET, mandatory CDK4/6i, ≤1 chemotherapy to (345 mg daily) or (aromatase fulvestrant). PFS was assessed across post hoc exploratory analyses without adjustment for multiple testing. Results: months, median 8.6 1.9 months (HR, 0.41; 95% confidence interval, 0.26–0.63). this population, (in months) 9.1 (bone metastases), 7.3 (liver and/or lung 9.0 (&lt;3 sites), 10.8 1.8 (≥3 5.5 (PIK3 catalytic subunit α mutation), (tumor protein p53 gene (HER2-low), (ESR1D538G-mutated tumors), (ESR1Y537S/N-mutated tumors). Subgroup consistent overall population. Conclusions: The associated clinically meaningful improvement compared all HER2−, tumors.

Language: Английский

Citations

18
Pathological complete response rate and disease-free survival after neoadjuvant chemotherapy in patients with HER2-low and HER2-0 breast cancers DOI Creative Commons
Alexandre de Nonneville, Gilles Houvenaeghel, Monique Cohen

et al.

European Journal of Cancer, Journal Year: 2022, Volume and Issue: 176, P. 181 - 188

Published: Sept. 28, 2022

Half of HER2-negative breast cancers (BC) show HER2-low expression. The strong efficacy recent anti-HER2 antibody-drug conjugates (ADC) in tumours has risen the interest as a proper BC subtype. Chemosensitivity and prognosis this subtype are not clear when compared to HER2-0 tumours. We investigated pathological complete response (pCR) disease-free survival (DFS) rates patients receiving neoadjuvant chemotherapy for or tumours.Data were collected from Institut Paoli-Calmettes database. defined by HER2 IHC score 1+ 2+ with negative FISH, 0. Clinicopathological characteristics, pCR (defined [ypT0/ypTis] [pN0sn ypN0]) DFS between two cohorts.From Jan/2005 Jun/2021, 1111 evaluable. incidence was 41%, including 63% hormone receptor (HR)-positive 37% HR-negative (p < 0.001). In whole population, rate lower (23%) versus (30%) = 0.013), but association lost multivariate analysis. HR-positive patients, negatively impacted (10% vs. 16%, p 0.046), HR-negatives (46% 42%), result maintained No correlation existed HER2-status.HER2-low is associated HR positivity. status did impact whereas patients.

Language: Английский

Citations

52
Current Biological, Pathological and Clinical Landscape of HER2-Low Breast Cancer DOI Open Access

Huina Zhang,

Yan Peng

Cancers, Journal Year: 2022, Volume and Issue: 15(1), P. 126 - 126

Published: Dec. 25, 2022

HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC that has HER2 immunohistochemical (IHC) score 1+ or 2+/in situ hybridization (ISH) negative phenotype. Recent clinical trials have demonstrated significant benefits novel directing antibody-drug conjugates (ADCs) in treating this group tumors. Trastuzumab-deruxtecan (T-Dxd), HER2-directing ADC was recently approved by the U.S. Food and Drug Administration as first targeted therapy to treat BC. However, still not well characterized clinically pathologically. This review aims update current biological, pathological landscape based on English literature published past two years propose future directions management, pathology practice, translational research We hope it would help better understand tumor biology efforts for identifying recognized targetable

Language: Английский

Citations

47
Comparison of HER2-zero and HER2-low in terms of clinicopathological factors and survival in early-stage breast cancer: A systematic review and meta-analysis DOI
Yakup Ergün, Gökhan Uçar, Baran Akagündüz

et al.

Cancer Treatment Reviews, Journal Year: 2023, Volume and Issue: 115, P. 102538 - 102538

Published: March 6, 2023

Language: Английский

Citations

41
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

39
HER2-Low Breast Cancer: a New Subtype? DOI
Chiara Corti, Federica Giugliano, Eleonora Nicolò

et al.

Current Treatment Options in Oncology, Journal Year: 2023, Volume and Issue: 24(5), P. 468 - 478

Published: March 27, 2023

Language: Английский

Citations

34
Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer DOI Creative Commons
Tatjana Geukens, Maxim De Schepper, François Richard

et al.

European Journal of Cancer, Journal Year: 2023, Volume and Issue: 188, P. 152 - 160

Published: May 6, 2023

Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay the primary tumour or small biopsy. We assessed intra-patient inter-metastasis heterogeneity of status HER2-negative mBC.We included samples 10 patients (7 ER-positive and 3 ER-negative) donated context our post-mortem tissue donation program UPTIDER. Excisional biopsies 257 metastases 8 tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem samples. They were classified as HER2-zero, (HER2-1+ HER2-2+, situ hybridisation [ISH] negative) HER2-positive (HER2-3+ ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) HER2-ultralow (faint staining ≤10% cells).Median interval 2.5 h. In 8/10 patients, co-existed, with proportion lesions ranging from 5% to 89%. A total 32% currently HER2-ultralow. Intra-organ HER2-scores observed liver 3/6 patients. Patients disease had higher compared ER-negative (46% versus 8%, respectively). At metastasis level, percentages ER-expressing cells -ultralow metastases.Important exists. This questions validity its current form theranostic marker.

Language: Английский

Citations

30