Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials

Petrelli, Fausto; Ghidini, Antonio; Pedersini, Rebecca; Cabiddu, Mary; Borgonovo, Karen; Parati, Maria Chiara; Ghilardi, Mara; Amoroso, Vito; Berruti, Alfredo; Barni, Sandro

doi:10.1007/s10549-019-05133-y

Cited by 59 publications

(42 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…According to a recent meta-analysis including 3743 patients, the grade 3–4 toxicity profiles were similar between the three drugs. However, there was a lower risk of diarrhea for palbociclib compared to abemaciclib (relative risk, 0.13; 95% CI, 0.02 to 0.92; p = 0.04) as well as a reduced risk of prolonged QTc for palbociclib versus ribociclib (relative risk, 0.02; 95% CI, 0 to 0.83; p = 0.03) [94]. In conclusion, the three drugs are equally effective for the treatment of ER-positive HER2-negative breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

Sobhani

D’Angelo

Pittacolo

et al. 2019

Cells

108

View full text Add to dashboard Cite

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated.

show abstract

Section: Discussionmentioning

confidence: 99%

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

Sobhani

D’Angelo

Pittacolo

et al. 2019

Cells

108

View full text Add to dashboard Cite

show abstract

“…According to a recent meta-analysis including 3743 patients, the grade 3-4 toxicity profiles were similar between the three drugs. However, there was a lower risk of diarrhea for palbociclib compared to abemaciclib (relative risk, 0.13; 95% CI, 0.02-0.92; p= 0.04) as well as a reduced risk of prolonged QTc for palbociclib versus ribociclib (relative risk, 0.02; 95% CI, 0-0.83; p= 0.03) 92 . In conclusion, the three drugs are equally effective for the treatment of ER-positive HER2-negative breast cancer.…”

Section: Discussionmentioning

confidence: 93%

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

Sobhani¹,

D’Angelo²,

Pittacolo³

et al. 2019

Preprint

View full text Add to dashboard Cite

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

show abstract

“…Nonetheless, some discrepancies in their PK and CDKs isoforms selectivity need to be outlined. It can account for different response to treatment highlighted in some studies [ 17 ]. Differently from registration trials, in clinical practice all factors that may interfere with PK/PD and toxicological properties of investigated drugs and related to concomitant epidemiological, genetic and clinical conditions should be taken in consideration by clinicians.…”

Section: Introductionmentioning

confidence: 99%

CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions

Roncato

Angelini

Pani

et al. 2020

IJMS

View full text Add to dashboard Cite

Palbociclib, ribociclib, and abemaciclib belong to the third generation of cyclin-dependent kinases inhibitors (CDKis), an established therapeutic class for advanced and metastatic breast cancer. Interindividual variability in the therapeutic response of CDKis has been reported and some individuals may experience increased and unexpected toxicity. This narrative review aims at identifying the factors potentially concurring at this variability for driving the most appropriate and tailored use of CDKis in the clinic. Specifically, concomitant medications, pharmacogenetic profile, and pathophysiological conditions could influence absorption, distribution, metabolism, and elimination pharmacokinetics. A personalized therapeutic approach taking into consideration all factors potentially contributing to an altered pharmacokinetic/pharmacodynamic profile could better drive safe and effective clinical use.

show abstract

Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials

Cited by 59 publications

References 20 publications

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions

Contact Info

Product

Resources

About