Cyclin-dependent kinase 4/6 inhibitors as first-line treatment for post-menopausal metastatic hormone receptor-positive breast cancer patients: a systematic review and meta-analysis of phase III randomized clinical trials

Ramos-Esquivel, Allan; Hernandez-Steller, Hellen; Savard, Marie-France; Landaverde, Denis

doi:10.1007/s12282-018-0848-6

Cited by 31 publications

(38 citation statements)

References 25 publications

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“…To date, AIs have been the standard first‐line treatment for postmenopausal women with HR‐positive MBC . The recent approval of CDK4/6 inhibitors in combination with AIs for use in the first‐line setting largely occurred after the observation period of this study, and has the potential to change the treatment landscape; however, real‐world use has yet to be evaluated . Fulvestrant monotherapy continues to be an appropriate option for patients who have poor performance status or baseline neutropenia, which makes them poor candidates for CDK4/6 inhibitors .…”

Section: Discussionmentioning

confidence: 99%

“…The most recent phase 3 clinical studies have evaluated the effectiveness of CDK4/6 inhibitors in combination with AIs compared to AIs alone as first‐line therapy for HR‐positive MBC . A meta‐analysis of three phase 3 studies found that the use of CDK4/6 inhibitors in combination with AIs was associated with longer PFS compared to AI monotherapy (hazard ratio: 0.57, P < .001).…”

Section: Introductionmentioning

confidence: 99%

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Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

et al. 2019

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Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor‐positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor‐positive, human epidermal receptor 2‐negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real‐world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression‐free survival (PFS) and overall survival (OS). Patients were classified as ET‐naïve or by relapse status following adjuvant ET (“early” recurrence during or ≤12 months of completing adjuvant ET, or “late” >12 months after completing adjuvant ET). Outcomes were evaluated using Kaplan‐Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3 months (4.8‐12.3) for early relapse, 15.4 months (10.2‐21.2) for late relapse, and 18.7 months (10.1‐20.8) among ET‐naïve patients (P = .018). Median OS was 39.8 months (25.0‐55.1) for early relapse and 61.4 months (47.1‐61.4) for late relapse, but was not reached (NR; 55.6–NR) for ET‐naïve patients (P = .002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12 months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor‐positive MBC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

et al. 2019

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“…These drugs are always used with other inhibitors, especially AIs . In phase III randomized clinical trials, researchers showed that patients who combined AI and CDK4/6 inhibitors had higher progression‐free survival, overall response rates, and clinical benefit rates than did those who used AIs alone …”

Section: Inhibitors For Bc and Pcmentioning

confidence: 99%

“…106,107 In phase III randomized clinical trials, researchers showed that patients who combined AI and CDK4/6 inhibitors had higher progression-free survival, overall response rates, and clinical benefit rates than did those who used AIs alone. 108 HER2 was overexpressed in 20% of BC cases and associated with an aggressive phenotype and poor prognosis. 109 Trastuzumab, pertuzumab, and TDM-1, which are anti-HER2 antibodies, are Food and Drug Administration approved and can be used in clinics.…”

mentioning

confidence: 99%

Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer

Liu

Zhao

Zhang

et al. 2019

J of Cellular Biochemistry

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Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration‐dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen‐induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration‐resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.

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“…Other CDK4/6 inhibitors abemaciclib and ribociclib are under current FDA review for the approval of cancer treatment . The addition of CDK4/6 inhibitors (abemaciclib, palbociclib, or ribociclib) to anastrozole or letrozole significantly improved disease‐free survival, overall response rate, and clinical benefit rate in breast cancer, suggesting the combination of CDK inhibitors with other agents might be more effective for cancer treatment …”

Section: Biology and Regulation Of Cdks In Hccmentioning

confidence: 99%

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Shen

Dean²,

et al. 2019

Hepatology Research

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Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.

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Cyclin-dependent kinase 4/6 inhibitors as first-line treatment for post-menopausal metastatic hormone receptor-positive breast cancer patients: a systematic review and meta-analysis of phase III randomized clinical trials

Abstract: The addition of CDK 4/6 inhibitors (either abemaciclib, palbociclib, or ribociclib) to an AI (anastrozole or letrozole) significantly improved PFS, overall response rate, and clinical benefit rate in comparison with a nonsteroidal AI alone.

Cited by 31 publications

References 25 publications

Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

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