Efficacy of Fulvestrant in Women with Hormone-Resistant Metastatic Breast Cancer (mBC): A Canadian Province Experience

Abstract Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first- and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. The study aimed to assess the efficacy of fulvestrant in women with mBC in early- versus later-line therapy. Methods: In this retrospective cohort study, women with HR+ mBC who received fulvestrant between 2003–2019 in Saskatchewan were assessed. A multivariate Cox proportional survival analysis was performed. Results: 186 women with a median age of 63.5 years were identified; 178 (95.6%) had hormone resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤ 2-line-therapy, and 84 (45.2%) received ≥ 3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65) and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early- and later-line therapy in hormone-resistant mBC. Women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease had better survival.

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Efficacy of Fulvestrant in Women with Hormone-Resistant Metastatic Breast Cancer (mBC): A Canadian Province Experience

Cancers ◽

10.3390/cancers13164163 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4163

Author(s):

Samitha Andrahennadi ◽

Amer Sami ◽

Kamal Haider ◽

Haji Ibraheem Chalchal ◽

Duc Le ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Group ◽

Early Treatment ◽

Clinical Benefit ◽

Metastatic Breast ◽

Visceral Metastasis ◽

Hormone Receptor Positive ◽

Line Therapy ◽

Visceral Disease

Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first-and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. This study assessed the efficacy of fulvestrant in women with mBC in early-versus later-line therapy. Methods: This retrospective cohort study assessed Saskatchewan women with HR+ mBC who received fulvestrant between 2003–2019. A multivariate Cox proportional survival analysis was performed. Results: One hundred and eighty-six women with a median age of 63.5 years were identified—178 (95.6%) had hormone-resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤2-line-therapy, and 84 (45.2%) received ≥3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65), and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early-and later-line therapy in hormone-resistant mBC. Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival.

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Endocrine therapy or chemotherapy as first-line therapy in hormone receptor–positive HER2-negative metastatic breast cancer patients

European Journal of Cancer ◽

10.1016/j.ejca.2018.03.013 ◽

2018 ◽

Vol 95 ◽

pp. 93-101 ◽

Cited By ~ 14

Author(s):

E. Jacquet ◽

A. Lardy-Cléaud ◽

B. Pistilli ◽

S. Franck ◽

P. Cottu ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Hormone Receptor ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

First Line ◽

First Line Therapy ◽

Hormone Receptor Positive ◽

Line Therapy

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Phase I/II study of letrozole and sorafenib as first-line therapy of hormone-receptor positive (HR+) metastatic breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.531 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 531-531

Author(s):

Antoinette R. Tan ◽

Serena Tsan-Lai Wong ◽

Robert D. Warren ◽

Jennifer Eng-Wong ◽

Minetta C. Liu ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase I ◽

Hormone Receptor ◽

Metastatic Breast ◽

First Line ◽

First Line Therapy ◽

Hormone Receptor Positive ◽

Line Therapy

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Systemic treatment of hormone receptor positive, human epidermal growth factor 2 negative metastatic breast cancer: retrospective analysis from Leeds Cancer Centre

10.21203/rs.2.13299/v1 ◽

2019 ◽

Author(s):

Chris Twelves ◽

Sue Cheeseman ◽

Will Sopwith ◽

Matthew Thompson ◽

Majid Riaz ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Hormone Receptor ◽

Systemic Treatment ◽

Metastatic Breast ◽

Visceral Metastasis ◽

Hormone Receptor Positive ◽

Epidermal Growth

Abstract BACKGROUND Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies.METHODS Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012 - March 2018.RESULTS 196 women were identified with HR+/HER2- MBC. Median age was 67 years, 85.2% were post-menopausal and median time between primary diagnosis and metastasis was 5.4 years. Most (75.1%) patients received endocrine therapy as first line systemic treatment (1st LoT); use of 1st LoT chemotherapy halved between 2012 and 2017. Patients receiving 1st LoT chemotherapy were younger and more likely to have visceral metastasis (p<0.01). Median OS was 29.5 months and significantly greater for patients with exclusively non-visceral metastasis (p<0.01). The adjusted hazard ratio for death of patients with visceral (or CNS) metastasis was 1.91 relative to those with exclusively non-visceral metastasis.CONCLUSIONS Diverse endocrine therapies predominate as 1st LoT for patients with HR+/HER2- MBC, chemotherapy being associated with more aggressive disease in younger patients, emphasising the importance of using effective and tolerable therapies early.

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Outcome of palbociclib based therapy in hormone receptor positive metastatic breast cancer patients after treatment with everolimus.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1054 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1054-1054 ◽

Cited By ~ 1

Author(s):

Ajay Dhakal ◽

Christina Matthews ◽

Fan Zhang ◽

Ellis Glenn Levine ◽

Stephen B. Edge ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Endocrine Therapy ◽

Clinical Benefit ◽

Hormone Receptor ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Hormone Receptor Positive ◽

Metastatic Setting

1054 Background: Resistance mechanisms to CDK 4/6 inhibition are not well defined. Outcome data on hormone receptor positive (HR+) metastatic breast cancer patients (MBCP) treated with palbociclib (PA) after treatment with everolimus (EV) are lacking. The PALOMA 3 trial (P3) showing benefit of PA plus fulvestrant (FU) compared to FU in HR+ MBCP after progression on endocrine therapy excluded women previously treated with EV. The aim of our study was to investigate the outcomes of HR+ MBCP with prior EV treatment on PA based therapy. Methods: This is a retrospective, single institute review of HR+, HER 2 nonamplified MBCP from Jan 2014 - Nov 2016 treated with PA after treatment with EV. Women who received EV for < 1 month or PA < 14 days were excluded. Progression free survival (PFS) was defined as the time from the initiation of PA to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available radiological data. Clinical benefit was defined as a complete response (CR), partial response (PR) or stable disease of at least 24 weeks. Results: 23 patients with mean age 67 years (42 to 81) were identified. 95% were postmenopausal, 81% had ECOG performance status 0 or 1, 83% had visceral metastases, 95% had > 2 lines of prior endocrine therapy (ET), 82% shown prior sensitivity to ET, 82% received prior chemotherapy, of which 84% were in metastatic setting. Kaplan Meier estimate showed median PFS of 2.9 months (95% CI 2.0-4.2); median PFS of P3 PA cohort was 9.5 months (95% CI 9.2-11.0). Fisher’s exact test comparing study cohort with P3 PA cohort showed statistically significant differences in objective response (CR or PR) rates of 0/23 (0%) vs. 66/347 (19%, p = 0.02) & clinical benefit ratio of 4/23 (17.4%) vs. 231/347 (66.5%, p = 0.00). Conclusions: Outcomes with PA in HR+ EV treated MBCP were worse when compared to the P3 PA cohort data. Treatment with EV may lead to resistance to CDK inhibition. Though limited by size, our data suggests that use of PA after EV is associated with low response & clinical benefit rates. Further studies are necessary to confirm the findings to determine sequencing of targeted therapies.

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5048 A Q-TWiST analysis of lapatinib plus letrozole compared with letrozole alone as first-line therapy in hormone receptor positive (HR+) metastatic breast cancer (MBC)

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)70940-1 ◽

2009 ◽

Vol 7 (2) ◽

pp. 275

Author(s):

B. Sherrill ◽

M. Amonkar ◽

B. Sherif ◽

J. Maltzman ◽

L. O'Rourke ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Receptor ◽

Metastatic Breast ◽

First Line ◽

First Line Therapy ◽

Hormone Receptor Positive ◽

Line Therapy

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Combined ovarian ablation and aromatase inhibition as first-line therapy for hormone receptor-positive metastatic breast cancer in premenopausal women: report of three cases

Anti-Cancer Drugs ◽

10.1097/01.cad.0000224456.28898.37 ◽

2006 ◽

Vol 17 (8) ◽

pp. 999-1002 ◽

Cited By ~ 2

Author(s):

Nagi S. El-Saghir ◽

Ihab I. El-Hajj ◽

Jawad A. Makarem ◽

Zaher K. Otrock

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Premenopausal Women ◽

First Line ◽

Aromatase Inhibition ◽

Ovarian Ablation ◽

First Line Therapy ◽

Hormone Receptor Positive ◽

Line Therapy

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Hormone receptor–positive, HER2-negative metastatic breast cancer: redrawing the lines

Current Oncology ◽

10.3747/co.25.4000 ◽

2018 ◽

Vol 25 ◽

pp. 131 ◽

Cited By ~ 10

Author(s):

A. Matutino ◽

A.A. Joy ◽

C. Brezden-Masley ◽

S. Chia ◽

S. Verma

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Benefit ◽

Hormone Receptor ◽

Single Agent ◽

Treatment Algorithm ◽

Metastatic Breast ◽

Standards Of Care ◽

Endocrine Treatment ◽

Hormone Receptor Positive

Estrogen receptor modulators and estrogen deprivation have become standards of care for hormone receptor– positive metastatic breast cancer. However, after traditional first-line endocrine monotherapy treatment, the disease typically progresses despite the initial high rate of clinical benefit. Multiple studies have aimed at optimizing treatment strategies to improve upon clinical benefit beyond the traditional single-agent endocrine treatment. With the availability of new data and novel therapies, the clinical practice challenge becomes how best to define the optimal treatment sequence to maximize clinical benefit. In this review, we present treatment options clinically relevant to the management of hormone-positive, her2-negative metastatic breast cancer, and we propose a treatment algorithm based on the current literature.

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