fulvestrant

We report a case of luminal-type breast cancer with bone metastases and MSI-High, which was treated with PEM and showed a rapid therapeutic response.

P3, N=500, Not yet recruiting, AstraZeneca

P2, N=367, Active, not recruiting, Sanofi | Trial completion date: Mar 2024 --> Sep 2024

P1, N=42, Recruiting, Nanjing Chia-tai Tianqing Pharmaceutical | Not yet recruiting --> Recruiting

P2, N=90, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: May 2025 --> Apr 2032 | Trial primary completion date: May 2024 --> Apr 2027

Until 2023, fulvestrant was the only approved SERD; fulvestrant is administered intramuscularly, and in some cases may also have limited efficacy in the setting of certain ESR1 mutations. Elacestrant's recent approval sheds light on the use of biomarkers such as ESR1 to gauge a tumor's endocrine sensitivity. Ongoing therapeutic and correlative biomarker studies will offer new insight and expanding treatment options for patients with advanced breast cancer.

Finally, growth of ER-positive breast cancer cells in vivo was more potently inhibited by fulvestrant combined with the PFKFB3 inhibitor PFK158 than for each drug alone. In conclusion, these data suggest that PFKFB3 is identified as an adverse prognosis factor for ER-positive breast cancer and plays a previously unrecognized role in the regulation of ERα stability and activity. Our results further explores an effective approach to improve fulvestrant sensitivity through the early combination with a PFKFB3 inhibitor.

P2; Active, not recruiting --> Completed

P1/2, N=400, Recruiting, Scorpion Therapeutics, Inc. | Trial completion date: Apr 2028 --> Feb 2029 | Trial primary completion date: Apr 2026 --> Feb 2027

P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024

P1/2, N=18, Recruiting, Jonsson Comprehensive Cancer Center | Phase classification: P1b --> P1/2 | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025

P1, N=78, Recruiting, BeiGene | Not yet recruiting --> Recruiting

Inactivating WDR5 by knockdown or inhibitors phenocopies the effects of PML1 loss, reducing BCSC-related gene expression and tumorsphere formation and enhancing fulvestrant's anticancer activity. Our findings challenge the conventional understanding of PML as a tumor suppressor, redefine its role as a promoter of tumor growth in breast cancer, and offer new insights into the unique roles of PML isoforms in breast cancer.

P2, N=150, Not yet recruiting, Puma Biotechnology, Inc.

P3, N=495, Recruiting, Region Örebro County | Not yet recruiting --> Recruiting | Initiation date: Nov 2023 --> Mar 2024

P2, N=47, Recruiting, City of Hope Medical Center | Active, not recruiting --> Recruiting | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

P3, N=27, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=300 --> 27 | Trial completion date: Sep 2026 --> Nov 2024 | Trial primary completion date: Jun 2026 --> Nov 2024

Notably, capivasertib (AZD5363), a potent ATP-competitive Akt inhibitor, received FDA approval in November 2023 for use in combination with the estrogen receptor degrader fulvestrant to treat breast cancer. Challenges remain, including improving selectivity, identifying biomarkers to tailor treatments, and enhancing therapeutic efficacy while minimizing adverse effects. Particularly covalent-allosteric inhibitors hold promise for future more effective and personalized treatments.

P3, N=20, Terminated, Hoffmann-La Roche | Completed --> Terminated; The decision to not open the Phase III portion was based on a strategic sponsor decision and not driven by any safety concerns.

P1/2, N=240, Recruiting, Pfizer | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2026 --> Dec 2026

P1/2, N=337, Recruiting, Pfizer | Trial completion date: Oct 2027 --> May 2028 | Trial primary completion date: Aug 2026 --> Mar 2027

Combination therapy with TAT-PiET/TAT-PiET-PROTAC and JQ1, iJMJD6, or Fulvestrant exhibits synergistic effects. TAT-PiET or TAT-PiET-PROTAC treatment overcomes endocrine therapy resistance in ERα-positive breast cancer cells. Taken together, we demonstrated that targeting the ET domain is effective in suppressing breast cancer, providing a therapeutic avenue in the clinic.

In the phase III CAPItello-291 trial, capivasertib in combination with fulvestrant (C+F) demonstrated improved progression-free survival (PFS) (7.3 vs 3.1 months) compared with placebo-fulvestrant (P+F) cohort in AKT-altered pathway patients who had progressed through prior aromatase inhibitor. Capivasertib is a viable treatment option for patients with PIK3CA/AKT1/PTEN activating mutations following progression on endocrine-based regimens in the metastatic setting or recurrence within 12 months of completing adjuvant therapy. Integration of capivasertib into clinical practice is ongoing; intermittent dosing and favorable toxicity are attractive for future novel combination prospective trials.

Gedatolisib plus palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of-care therapies and had an acceptable safety profile.

P2, N=1163, Recruiting, The First Affiliated Hospital with Nanjing Medical University

EB1089 significantly enhanced the cell growth inhibitory effect of lapatinib combined with antiestrogens in HER2-positive breast cancer cells by modulating ERα expression and Akt phosphorylation suppression. These results highlight the potential of this therapeutic approach as a promising strategy for managing HER2-positive breast cancer.

Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with T-DXd as second-line chemotherapy, was highly effective in a patient with HER2-positive stage IV breast cancer.

Approximately 177 mBC patients were enrolled, of whom 66 were treated with CD4/6 inhibitors plus letrozole and 111 were treated with CDK4/6 inhibitors and fulvestrant. Furthermore, neutropenia status was associated with a more than doubled risk of progression/death compared to patients without neutropenia (HR = 2.311; p = 0.025). Having identified certain factors that could be associated with the development of neutropenia and considering that neutropenia itself is associated with an increased risk of progression, we believe that the baseline characteristics should be taken into account to reduce cases of neutropenia and disease progression.

P1, N=256, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting

Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.

A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38 months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21 months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40 mg/body epirubicin on day 1, 4 mg/body mitomycin C on days 1 and 15, and 500 mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses)...Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.

P1, N=198, Active, not recruiting, Eli Lilly and Company | Phase classification: P1b --> P1

The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.

P4, N=100, Recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=40, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Jun 2023 --> Mar 2025 | Trial primary completion date: Jun 2023 --> Mar 2025

P1/2, N=400, Recruiting, Scorpion Therapeutics, Inc. | N=220 --> 400 | Trial completion date: Jun 2026 --> Apr 2028

P2, N=60, Not yet recruiting, University of Washington | Trial completion date: Mar 2025 --> Jun 2026

P2, N=237, Completed, Eli Lilly and Company | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Nov 2023

In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival...Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor...In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

We've pioneered a nanoparticle system loaded with radioactive isotope 131I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer.

Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.