PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

Iwata, Hiroji; Im, Seock Ah; Masuda, Norikazu; Im, Young Hyuck; Inoue, Kentaro; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin; Zhang, Ke; Giorgetti, C.; Iyer, Shrividya; Schnell, Patrick; Bartlett, Cynthia Huang; Ro, Jungsil

doi:10.1200/jgo.2016.008318

Cited by 105 publications

(125 citation statements)

References 24 publications

(33 reference statements)

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“…As mentioned previously, tamoxifen (20 mg) is seen as having a low risk of QT prolongation, including when in combination with QT‐prolonging agents. Despite this, in MONALEESA‐7, an unexpected higher incidence of notable Fridericia's corrected QT interval (QTcF) values was observed in patients in both the placebo plus tamoxifen and ribociclib plus tamoxifen arms compared with those receiving a nonsteroidal aromatase inhibitor . Very few patients discontinued ribociclib or palbociclib or required a dose reduction because of QT prolongation, and no clinical symptoms of QT prolongation or cases of Torsades de pointes were reported .…”

Section: Resultsmentioning

confidence: 99%

Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer

et al. 2019

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Cardiac monitoring is becoming an important part of breast cancer care. Breast cancer and cardiovascular disease (CVD) share many common risk factors, and it is estimated that by the median age of diagnosis, many patients with breast cancer will have established or subclinical CVD. In addition, a number of treatments for metastatic breast cancer are known to have cardiac effects. As such, there is a clear need to prevent, identify, and effectively manage cardiovascular events in patients with breast cancer. Current clinical practice for patients with metastatic breast cancer involves a comprehensive set of assessments to ensure efficacy and safety of treatment. Adding cardiac monitoring to the assessments already required for patients with breast cancer may improve survival and quality of life. Currently, cardiac monitoring is recommended for several breast cancer treatments, and guidelines related to cardiac monitoring are available. Here, we review the risk of CVD in patients with breast cancer, providing an overview of the cardiac events associated with standard therapies for metastatic breast cancer. We also assess the current clinical recommendations relating to cardiac monitoring, and practical management strategies for oncologists. Cardio‐oncology is a growing medical subspecialty that promotes the need for effective cancer therapy while minimizing cardiac effects. Integrating cardiac monitoring into routine clinical practice may safeguard patients with metastatic breast cancer against adverse cardiac effects. Implications for Practice This review details the common risk factors associated with cardiovascular disease that are frequently observed in patients with metastatic breast cancer, as well as the adverse cardiac effects of many therapies that are commonly prescribed. The review also provides a rationale for routine and comprehensive cardiovascular assessment of all patients at baseline, and during and after therapy depending on the treatment and presence of risk factors for cardiovascular disease. The medical discipline of cardio‐oncology is increasingly being recognized as an important part of clinical practice to ensure effective cancer therapy while maintaining cardiac health.

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Section: Resultsmentioning

confidence: 99%

Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer

et al. 2019

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“…Newer hormonal agents have improved outcomes to some degree, but combination therapies of hormonal agents with agents targeting other pathways may enhance outcomes further in patients with advanced disease. This approach has been successful in the second‐line setting following prior endocrine resistance, where median PFS was shown to have not been reached with a combination of palbociclib plus fulvestrant vs 5.8 months with placebo plus fulvestrant (HR, 0.49; 95% CI, 0.27‐0.87; P < .01) in premenopausal and postmenopausal Asian patients (n = 72) with advanced ER+ breast cancer …”

Section: Discussionmentioning

confidence: 99%

Palbociclib in combination with letrozole as first‐line treatment for advanced breast cancer: A Japanese phase II study

Masuda

Nishimura²,

Takahashi

et al. 2018

Cancer Science

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This single‐arm, open‐label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative (ER+/HER2−) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first‐line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). Primary endpoint of investigator‐assessed 1‐year progression‐free survival (PFS) probability was 75.0% (90% CI, 61.3%‐84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy. Median duration of treatment was 438 days. Among secondary efficacy measures, median PFS was not reached (95% CI, 16.7: not estimable), 17/42 patients (40.5%) had an objective response, 36/42 (85.7%) maintained disease control, and 27/42 (64.3%) remained in follow‐up. Median overall survival was not reached, and 1‐year survival probability was 92.9% (95% CI, 79.5%‐97.6%). Results of intensive pharmacokinetics in a subset of 6 patients showed palbociclib steady‐state mean area under the plasma concentration‐time curve over the dosing interval [τ] and mean maximum plasma concentration were 1979 ng·h/mL and 124.7 ng/mL, respectively. For day 15 plasma samples from cycles 1 and 2, geometric mean of the within‐patient mean trough concentration was 90.1 ng/mL. The most common treatment‐related adverse events were neutropenia (100%) and stomatitis (73.8%). There was 1 case of treatment‐related febrile neutropenia. Toxicities were generally tolerated and manageable by dose modifications and/or medical care. Efficacy and safety of first‐line palbociclib plus letrozole therapy is supported in Japanese postmenopausal patients with treatment‐naive ER+/HER2− advanced breast cancer.

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“…Currently, fulvestrant is the only and so-called "pure anti-oestrogen" oestrogen receptor downregulator without any agonist effects. In advanced HR-positive breast tumour patients, fulvestrant is often used in combination with a cyclindependent kinase 4 and 6 (CDK4/6) inhibitor, which can significantly prolong progression-free survival compared to fulvestrant alone (9.2 months vs 3.5 months; P = 0.007) [40]; in patients sensitive to endocrine therapy, this combination therapy also brings about longer OS than fulvestrant monotherapy (39.7 months vs 29.7 months; Hazard ratio, 0.92; 95% CI, 0.55-0.94) [41]. In postmenopausal women, the most oestrogen is produced via androstenedione synthesized from adrenal gland enters into peripheral adipose tissue that is converted to oestrogen by 17-hydroxysteroid dehydrogenase [42].…”

Section: Discussionmentioning

confidence: 99%

The tumour response of postmenopausal hormone receptor-positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis

Wang

Song

et al. 2020

BMC Women's Health

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Background: To investigate the efficacy of neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET) and neoadjuvant chemoendocrine therapy (NCET) on the tumour response, including pathological complete response (pCR) rate and overall response rate (ORR), in postmenopausal women with hormone receptor (HR)-positive breast cancer. Methods: Based on a PRISMA-IPD statement, the PubMed, Embase and Cochrane Library databases were used to identify eligible trials published from inception to 7 May 2019. Pooled odds ratio (OR) with 95% confidential interval (CI) was calculated to assess the pCR rate and ORR of tumours among those three treatments via fixed-or randomeffect Mantel-Haenszel models in terms of a Heterogeneity Chi 2 test with a significant level of p < 0.1. All statistical tests were performed by the software of StataSE, version 12.0. Results:The analysed data consisted of 10 eligible clinical trials with 971 unique HR-positive breast cancer patients. The pooled results indicated that the pCR rate of those patients undergoing NET was significantly lower than those undergoing NCT (pooled OR, 0.48; 95% CI, 0.26-0.90), whereas the difference of ORR between both therapies was not statistically significant (pooled OR, 1.05; 95% CI, 0.73-1.52). The combined paradigm of NCET compared with the monotherapy of NET or NCT did not present a significantly improved pCR rate or ORR (pooled OR, 2.61; 95% CI, 0.94-7.25; and 2.25; 95% CI, 0.39-13.05; respectively).Conclusion: Postmenopausal HR-positive breast cancer patients after NCT may have better tumour response than those after NET, while those undergoing NCET may not manifest the apparently improved clinical efficacies compared to those receiving monotherapy.

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Cited by 105 publications

References 24 publications

Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer

Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer

Palbociclib in combination with letrozole as first‐line treatment for advanced breast cancer: A Japanese phase II study

The tumour response of postmenopausal hormone receptor-positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis

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