LBA20 Open-label, randomized study of lasofoxifene (LAS) vs fulvestrant (Fulv) for women with locally advanced/metastatic ER+/HER2- breast cancer (mBC), an estrogen receptor 1 (ESR1) mutation, and disease progression on aromatase (AI) and cyclin-dependent kinase 4/6 (CDK4/6i) inhibitors

Goetz, Matthew P.; Plourde, P.; Stover, Daniel G.; Bagegni, Nusayba A.; Vidal, GA; Brufsky, Adam; Rugo, HS; Portman, D.J.; Gal‐Yam, Einav Nili

doi:10.1016/j.annonc.2022.08.015

Cited by 17 publications

(14 citation statements)

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“…Given the small sample size of just 103 randomized patients, the hazard ratio at 0.699 (95 % CI: 0.445-1.125; p = 0.138) was not statistically significant; nevertheless, it was highly promising. The median PFS in this therapy-resistant context was increased from 4.04 months to 6.04 months [27].…”

Section: Elainementioning

confidence: 92%

See 1 more Smart Citation

Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer

Lüftner¹,

Lux²,

Fehm

et al. 2023

Geburtshilfe Frauenheilkd

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Large-scale study programs on CDK4/6 inhibitors, targeted therapies, and antibody–drug conjugates launched in recent years have yielded results from current studies which are now being published in journals and presented at international conferences. In this context, new results are available from the major CDK4/6 inhibitor studies. Also, an increasing amount of data is being published from large-scale genomic studies on efficacy and resistance mechanisms in patients treated with CDK4/6 inhibitors. These results now form the basis for further research plans to investigate combination therapies and treatment sequencing. Based on the latest published results, sacituzumab govitecan is now available as a second antibody–drug conjugate; this brings an advantage in terms of overall survival for patients with hormone receptor-positive (HRpos)/HER2-negative (HER2neg) breast cancer. In this review article, we summarize the latest developments and place them in context according to the current status of research.

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Section: Elainementioning

confidence: 92%

“…Mit einer kleinen Fallzahl von 103 randomisierten Patientinnen war die Hazard Ratio mit 0,699 (95 %-KI: 0,445-1,125; p = 0,138) zwar nicht statistisch signifikant, aber vielver-sprechend. Das mediane PFS wurde in dieser therapieresistenten Situation von 4,04 Monate auf 6,04 Monate verlängert [27].…”

Section: Elaineunclassified

Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer

Lüftner¹,

Lux²,

Fehm

et al. 2023

Geburtshilfe Frauenheilkd

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show abstract

“…Lasofoxifene demonstrated interesting activity in the clinical trial ELAINE 1 in which it was compared with fulvestrant in ESR1 -mutated MBC patients with progression on CDK4/6i, and all clinical outcomes were in favored lasofoxifene. The association of lasofoxifene with abemaciclib, in phase II trial ELAINE 2, showed efficacy in heavily pretreated patients with ESR1 -mutated MBC post-CDK4/6i (ASCO 2022) [ 57 ]. Bazedoxifene (Duavive ® ) is a synthetic SERM, which received approval by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women.…”

Section: Breast Cancer Therapiesmentioning

confidence: 99%

Targeting Breast Cancer: An Overlook on Current Strategies

Iacopetta

Ceramella

Baldino

et al. 2023

IJMS

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Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause of cancer death among women worldwide. Globally, BC is the second most frequent cancer and first most frequent gynecological one, affecting women with a relatively low case-mortality rate. Surgery, radiotherapy, and chemotherapy are the main treatments for BC, even though the latter are often not aways successful because of the common side effects and the damage caused to healthy tissues and organs. Aggressive and metastatic BCs are difficult to treat, thus new studies are needed in order to find new therapies and strategies for managing these diseases. In this review, we intend to give an overview of studies in this field, presenting the data from the literature concerning the classification of BCs and the drugs used in therapy for the treatment of BCs, along with drugs in clinical studies.

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“…Other novel ET agents in development include the proteolysis targeting chimera (PROTAC) ARV-471 ( Hurvitz et al, 2022 ), the complete ER antagonist (CERAN) OP-1250 ( Patel et al, 2022 ), the selective ER covalent antagonists (SERCA) H3B 6545 ( Johnston et al, 2022 ), the third-generation selective ER modulator (SERM) lasofoxifene ( Goetz et al, 2022a ; Damodaran et al, 2022 ), and the ShERPA (selective human ER partial agonists) TTC-352 ( Dudek et al, 2020 ). These agents have demonstrated encouraging anti-tumor activity in early phase trials which have included patients treated previously with a CDK4/6 inhibitor ( Supplementary Table S1 ).…”

Section: Therapeutic Strategies Following Progression On Cdk4/6 Inhib...mentioning

confidence: 99%

CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective

Zhou

Downton

Freelander

et al. 2023

Front. Cell Dev. Biol.

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CDK4/6 inhibitors have become game-changers in the treatment of estrogen receptor-positive (ER+) breast cancer, and in combination with endocrine therapy are the standard of care first-line treatment for ER+/HER2-negative advanced breast cancer. Although CDK4/6 inhibitors prolong survival for these patients, resistance is inevitable and there is currently no clear standard next-line treatment. There is an urgent unmet need to dissect the mechanisms which drive intrinsic and acquired resistance to CDK4/6 inhibitors and endocrine therapy to guide the subsequent therapeutic decisions. We will review the insights gained from preclinical studies and clinical cohorts into the diverse mechanisms of CDK4/6 inhibitor action and resistance, and highlight potential therapeutic strategies in the context of CDK4/6 inhibitor resistance.

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LBA20 Open-label, randomized study of lasofoxifene (LAS) vs fulvestrant (Fulv) for women with locally advanced/metastatic ER+/HER2- breast cancer (mBC), an estrogen receptor 1 (ESR1) mutation, and disease progression on aromatase (AI) and cyclin-dependent kinase 4/6 (CDK4/6i) inhibitors

Cited by 17 publications

References 0 publications

Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer

Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer

Targeting Breast Cancer: An Overlook on Current Strategies

CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective

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