letrozole

P=N/A, N=419, Completed, MedSIR | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> May 2024

P2, N=200, Recruiting, Oana Danciu | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2024 --> Aug 2028

P=N/A, N=884, Not yet recruiting, The University of Hong Kong

These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned.

P3, N=463, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Jan 2026

Notably, the combined approach of ET and CDK4/6 inhibitor represents a novel intervention in managing DCBM in patients with LBC.

Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and molecular profile.

P2, N=65, Active, not recruiting, Jules Bordet Institute | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Aug 2024 --> Jan 2025

P1, N=53, Completed, Rovi Pharmaceuticals Laboratories | Active, not recruiting --> Completed | N=120 --> 53

P2/3, N=260, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

Cyclin D-dependent kinase 4/6 inhibitors palbociclib, ribociclib and abemaciclib, in combination with aromatase inhibitors anastrozole and letrozole or oestrogen receptor degrader fulvestrant, are being assessed as candidates for therapeutic drug monitoring. DLLME proved to be the most ecologically acceptable method due to the high degree of miniaturisation (AGREEprep score 0.44), PLR enabled very high sample throughput and cost-effectiveness (BAGI 72.5), while SPE showed the best analytical performance (redness score 100). All three methods are suitable for their designated purpose, and the choice of the ideal method can be made based on the scope of application, available funds and equipment and desired ecological footprint.

Both in vitro and in vivo studies demonstrated that a combination of Lapa@HSA(VE) NPs and Let@HSA(VE) NPs in the ratio 75:25 inhibited tumor development and enhanced apoptosis significantly compared to individual NP treatment and free drug. The combination NPs therapy exhibited significant efficacy even in Lapa-resistant cell lines.

Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jul 2024 --> Jan 2025

To determine the test's utility in identifying which patients with EBC in the IDEAL (Investigation on the Duration of Extended Adjuvant Letrozole) trial could benefit from 5-year vs 2.5-year letrozole treatment...These findings suggest that this gene expression assay could go beyond guiding neoadjuvant and adjuvant chemotherapy decisions to informing the optimal duration of adjuvant endocrine therapy. EU Clinical Trials Register Eudra CT: 2006-003958-16.

Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA.Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.

LTP in layer 4 to layer 2/3 synapses in the somatosensory cortex was also reduced in slices from letrozole-treated mice, showing deficits in structural and functional plasticity resulting from aromatase inhibition. Ovariectomized mice performed worse than intact control mice in the novel object recognition test but, surprisingly, letrozole treatment rescued this deficit.

After receiving capecitabine, lapatinib, gonadotropin-releasing hormone (GnRH) agonist, and tamoxifen, multiple new lesions appeared in the brain after 14 months. The patient then received capecitabine, neratinib, GnRH agonist, and letrozole; however, her brain metastases still progressed after 7 months...Now aged 30, the patient is continuing to receive T-DXd treatment to prevent recurrence. We conclude that T-DXd was effective for the treatment of brain metastases in this young patient with triple-positive metastatic breast cancer who had multiple risk factors and had received several anti-HER2 therapies prior to T-DXd.

P3, N=3832, Not yet recruiting, Region Örebro County | Initiation date: May 2024 --> Jan 2025

Promising derivatives revealing low damage to healthy cells were subject to enzymatic inhibitory assessment against ARO and EGFR and their activities compared to letrozole and erlotinib respectively...Eventually, molecular docking analysis revealed that hit compounds 3c, 4c, 4d, and 6a could bind favorably to the proposed in silico models of various protein-ligand interactions. Therefore, our promising top candidates, by demonstrating appreciable anti-breast cancer activities, present valuable prospects for optimization, potency enhancement and future application.

Introduction The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. Conclusion The INGE-B trial demonstrated good efficacy and tolerability of PAL with letrozole (1L) or fulvestrant (first and later line) in accordance with the PALOMA-trials. In addition, the so far lacking proof of efficacy and safety of PAL in combination with anastrozole or exemestane in 1L and with letrozole in later line was provided by INGE-B.

In contrast, anastrozole and letrozole show lower binding affinities for HER2 and EGFR due to their simpler structures but are potent aromatase inhibitors, making them effective in treating estrogen receptor-positive (ER-positive) breast cancers. In conclusion, DFT and molecular docking studies affirm the suitability of lapatinib, tucatinib, and neratinib for HER2-positive cancers, while anastrozole and letrozole are effective in ER-positive cancers, emphasizing the role of molecular structure and binding affinity in optimizing cancer treatment strategies.

P4, N=40, Recruiting, The First Affiliated Hospital of Chongqing Medical University; The First Affiliated Hospital of Chongqing Medical University

P4, N=40, Not yet recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

P2, N=130, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Aug 2029 --> Aug 2030 | Trial primary completion date: Aug 2026 --> Aug 2027

P1, N=17, Active, not recruiting, Peter MacCallum Cancer Centre, Australia | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=90, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2026 --> Jun 2025

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

P3, N=1156, Not yet recruiting, Alliance for Clinical Trials in Oncology

"The first 120 postmenopausal participants (60 with invasive ductal carcinoma [IDC] and 60 with invasive lobular carcinoma [ILC]) were randomized to letrozole versus tamoxifen for a 2-week window phase; all patients were then randomized 2:1 to a 24-week treatment phase of NET +/- Palbociclib (Palbo). Among patients treated with NET +/- Palbo, 43.6% of whom had ILC, 57.8% exhibited CCA. Most patients with available PAM50 results had luminal B subtype (61.3%). Cell cycle arrest after NET and baseline intrinsic subtype did not correlate with ypN status among patients treated with NET +/- Palbo."

Pts with HR+ HER2- aBC from a phase II trial of an alternative schedule of palbociclib (palbo alt dosing trial NCT 3007979) and from a retrospective CDK4/6i study were included in this analysis...The majority of these pts received palbo (10/10) paired with letrozole (8/10) and did not have recurrence on adjuvant endocrine therapy (8/10)... Early progression on CDK4/6i is associated with a particularly poor prognosis; however, there are patients with exceptional response to CDK4/6i who may remain on therapy for an extended time. There were variations in the mutation profiles between the two cohorts, though this data set was limited in size. Additional analysis of genomic variants is needed to identify profiles of patients who may significantly benefit from CDK4/6i.

57.14% (4/7) received adjuvant Letrozole for a minimum of 5 years. The patient with a recurrence score of 24 received adjuvant chemotherapy and developed metastatic 4 years post diagnosis while on Tamoxifen...Genomic tests have resulted in a significant reduction in the number of patients receiving adjuvant chemotherapy. However, a more multifacted approach may be required to tailor treatment decisions incorporating genomic testing, clinicopathological features and individual characteristics with the aim of improving outcomes for patients with hormone receptor positive early breast cancer.

Hormonal therapy consisted of letrozole for post-menopausal patients and tamoxifen plus LH-RH agonist for pre/peri-menopausal patients. Neoadjuvant endocrine therapy for 16 weeks changes subtype classification by PAM50 from luminal B to luminal A and the ROR drastically. Greater effects were noted for the combination, not statistically significant, but this warrants further investigation in a larger cohort. There were 3 HER2-enriched cases with poor response, but this was not significant because of the small sample size.

Overall, CDKi+ET had been administered in 1st, 2nd and ≥3rd line in 65.1%, 14.8% and 20.1% cases, with 54.0% patients progressing to ribociclib as CDKi and 57.1% progressing to letrozole as ET. Subtype switching towards less ET-sensitive IS, especially the HER2E, occurs under CDKi+ET and has prognostic value. Post-CDKi LumA disease showed the best outcomes, regardless of treatment type. This group of patients might be the ideal group to be treated with ET-based therapies.

Methods Pre/perimenopausal pts with no prior systemic therapy for aggressive HR+/HER2− ABC were randomized 1:1 to RIB + letrozole/anastrozole + goserelin or physician's choice of combo CT. Contrary results in the CT arm suggest that these signatures warrant further studies on their potential predictive value. These data are hypothesis generating and should be interpreted with caution due to small sample sizes.

This is a retrospective study of paired samples from patients (pts) with hormone receptor-positive and HER2-negative (HR+/HER2-) EBC treated at Hospital Clinic of Barcelona between 2014 and 2023 and from the letrozole arm of SOLTI-1501 VENTANA trial (Adamo et al...All pts received POET for 2 to 12 weeks prior to surgery, with tamoxifen or aromatase inhibitors (AI), administered according to menopausal status... POET is a simple and secure treatment that can be administrated before surgery in HR+/HER2- EBC. The molecular profiling and dynamic evaluation of biological changes induced by POET could offer opportunities for a better understanding of the tumor´s sensitivity to endocrine therapy and could help guide and optimize treatment strategies in HR+/HER2- EBC.

Therapies targeting mutations in this pathway approved in conjunction with endocrine therapy include alpelisib, everolimus and capivasertib...She received nab-paclitaxel/atezolizumab for 4 months, letrozole and abemaciclib for 2 months, letrozole alone for 6 months, and letrozole and ribociclib for 6 weeks. Given presence of PIK3CA mutation, 4th line treatment with fulvestrant and alpelisib was planned...After progressing on capecitabine after 2 months, alpelisib with exemestane was initiated...Due to a low ejection fraction despite work with cardiooncology, she was not a candidate for trastuzumab deruxtecan. She progressed on oral cyclophosphamide and methotrexate after 2 months and Sacituzumab govitecan after 3 months...Comprehensive biomarker assessment is needed to identify patients who may benefit from sequential therapies. There is a need for trials comparing therapies that target the PI3K pathway at distinct points, potential sequencing of these therapies, and the optimal sequence strategy.

Neoadjuvant let/abema and CT varied in efficacy by Recurrence Score®. Let/abema achieved higher CCCA rates in RS≤25 patients, accompanied by significant ER and PgR mRNA suppression, highlighting its efficacy in less biologically aggressive subtypes and suggesting it might replace the need for CT. Surgery-RS result was higher in the let/abema arm than in CT and correlated inversely with surgery ER and PgR levels, indicating deeper ER signaling suppression.

She remained with no evidence of disease on tucatinib, trastuzumab, and capecitabine for over 19 months but developed severe hand-foot syndrome...The pt's capecitabine dose was increased, and letrozole was added as her resected brain metastasis showed positive progesterone receptor expression... This study describes real-world use and results of a tissue-free monitoring test in early-stage BC. The high QC pass rate (99.9%) and rapid 10-day TAT support the feasibility of a tissue-free assay for MRD detection. Results suggest a potential provider preference for monitoring for patients with stage III BC, TNBC, and HR-/HER2+ BC.

Pts were randomized 2:2:1 to: (A) HER3-DXd 5.6 mg/kg every (Q) 21 days (D) for 6 cycles; (B) HER3-DXd plus QD LET (+/- LHRH agonist); (C) CT with 4 cycles of EC/AC (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 Q14 or 21 D) followed by weekly paclitaxel 80mg/m2 for 12 weeks. In SOLTI VALENTINE, treatment with HER3-DXd, with or without LET, resulted in similar pCR rates to CT, while exhibiting a lower incidence of grade ≥3 TEAEs. CelTIL score at C2D1 correlated with response to HER3-DXd, but not to CT. The ongoing translational analysis, as well as the survival outcomes of VALENTINE, will provide further insights into the activity of HER3-DXd in EBC and clarify its potential role as a treatment strategy for high-risk HR+/HER2-neg breast cancer.

Furthermore, the side effects were manageable and no dose reductions were necessary during treatment. These findings suggest that the combination of CDK4/6i and ET in the treatment of HR+/HER2-advanced breast cancer cannot be underestimated.

P2, N=47, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting