CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis

Gao, Jennifer; Cheng, Joyce; Bloomquist, Erik; Sanchez, Jacquelyn; Wedam, Suparna; Singh, Harpreet; Amiri‐Kordestani, Laleh; Ibrahim, Amna; Sridhara, Rajeshwari; Goldberg, Kirsten B.; Theoret, Marc R.; Kluetz, Paul G.; Blumenthal, Gideon M.; Pazdur, Richard; Beaver, Julia A.; Prowell, Tatiana M.

doi:10.1016/s1470-2045(19)30804-6

Cited by 217 publications

(187 citation statements)

References 21 publications

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“…This behavior relies on the diffused perception, among both oncologists and patients, that chemotherapy is a more potent treatment, yielding on average a higher ORR than ET-based treatments. In contrast, our meta-analysis, as well as the previous ones [56][57][58][59] confirms that the combination of CDK4/6 inhibitors and ET yields a very high rate of tumour regression, which is on average as high as 55% for patients with measurable disease, with no heterogeneity among different compounds. To the best of our knowledge, this ORR is higher than we would expect with mono-chemotherapy and comparable (but still lower) to what we would expect with an aggressive polychemotherapy in HR+ patient populations.…”

Section: Discussionsupporting

confidence: 73%

Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

Piezzo

Chiodini

Riemma

et al. 2020

IJMS

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The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

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Section: Discussionsupporting

confidence: 73%

Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

Piezzo

Chiodini

Riemma

et al. 2020

IJMS

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“…The introduction of CDK4/6 inhibitors in clinical practice represents a major advancement for the treatment of HR-positive HER2-negative BC ( Table 1). The combination of CDK4/6i and ET seems to be effective in all clinicopathological subgroups, as emerged by the large pooled analysis of FDA [138]. Preclinical and translational research is now exploring the heterogeneous landscape able to drive the response to these agents.…”

Section: Discussionmentioning

confidence: 99%

Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors

Piezzo

Cocco

Caputo

et al. 2020

IJMS

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Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment.

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“…The US Food and Drug Administration performed a pooled analysis of all 7 phase 3 trials using CDK4/6 inhibitors. 2 They examined 4200 participants who received a CDK4/6 inhibitor in combination with an aromatase inhibitor in the frontline setting or with fulvestrant in any setting.…”

mentioning

confidence: 99%

In Support of CDK4/6 Inhibitors—A Meta-analysis of Available Randomized Data

Martin

Goldstein

2020

JAMA Netw Open

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The recent development of inhibitors of cyclin dependent kinases 4 and 6 (CDK4/6) is arguably one of the most clinically important discoveries for patients living with hormone receptor (HR)-positive, ERBB2 (formerly HER2)-negative metastatic breast cancer. Currently, there are 3 available CDK4/6 inhibitors: palbociclib, ribociclib, and abemaciclib. These CDK4/6 inhibitors induce cell cycle arrest by preventing the G1 to S phase transition, and they are often administered in combination with endocrine therapy (ET). Li et al 1 performed a meta-analysis of the 9 published randomized clinical trials that compared ET plus either a CDK4/6 inhibitor or placebo. Eight phase 3 clinical trials were included as well as 1 randomized phase 2 study. Phase 1 trials, retrospective studies, and those without overall survival (OS) outcomes were not included in their analysis.

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CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis

Cited by 217 publications

References 21 publications

Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors

In Support of CDK4/6 Inhibitors—A Meta-analysis of Available Randomized Data

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