Search results for "Palbociclib"
showing 9 items of 19 documents
Targeted Therapies Overcoming Endocrine Resistance in Hormone Receptor-Positive Breast Cancer
2015
Breast cancer is a heterogeneous disease with different molecular subtypes. Most tumours are hormone receptor positive (luminal subtype) with potential endocrine responsiveness. Endocrine therapy is commonly used in these patients. Disease progression caused by endocrine resistance represents a significant challenge in the treatment of breast cancer. To understand the mechanisms of resistance of long-term oestrogen-deprived breast cancer cells, it is important to focus on cross-talk between steroid receptor signalling and other growth factor receptors and intracellular pathways. (Pre-)clinical trials showed that co-targeting these pathways can restore endocrine sensitivity. The focus of the…
A phase I/Ib study evaluating GDC-0077 (inavolisib) + palbociclib (palbo) + fulvestrant in patients (pts) with PIK3CA-mutant (mut), hormone receptor-…
2021
A randomized, open-label, multicentre, phase IV study evaluating palbociclib plus endocrine treatment versus a chemotherapy based treatment strategy …
2017
TPS1115 Background: Although endocrine based therapy is recommended as first-line treatment in metastatic breast cancer (MBC) in patients with an HER2-/HR+ tumour up to 50% of the patients receive chemotherapy. Palbociclib (P) a CDK4/6 inhibitor improves PFS by 42% in endocrine sensitive and resistant HER2-/HR+ MBC when added to an endocrine therapy (ET). Patients included in clinical trials are often criticised not to be representative for real world breast cancer patients. Methods: Patients with first-line HER2-/HR+ MBC who are candidate for mono-chemotherapy will be eligible to be randomised 1:1 to receive either P plus ET per label or mono-chemotherapy per investigator´s choice with or…
Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience
2019
Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At…
Abstract PS5-12: Preliminary correlative analysis of clinical outcomes with PIK3CA mutation (mut) status from a phase I/Ib study of GDC-0077 in patie…
2021
Abstract Background Mutations in p110α, encoded by PIK3CA, are present in ~40% of HR+/HER2- BCs. GDC-0077, a PI3Kα-selective inhibitor and mutant PI3Kα degrader, elicits antitumor activity in PIK3CAmut preclinical models as a single agent and when combined with endocrine therapy (ET). New evidence suggests BCs harboring multiple PIK3CAmut exhibit increased signaling through the PI3K/AKT pathway and are more sensitive to PI3Kα inhibitors compared with BCs with a single PIK3CAmut. We report a preliminary analysis of PIK3CAmut status with clinical outcomes from an ongoing study of GDC-0077 alone or with ET (letrozole/fulvestrant) ± palbociclib (palbo) in pts with PIK3CAmut HR+/HER2- mBC (NCT03…
Abstract PS11-05: Updated data from SERENA-1: A Phase 1 dose escalation and expansion study of the next generation oral SERD AZD9833 as a monotherapy…
2021
Abstract Background: AZD9833 is an oral selective estrogen receptor (ER) antagonist and degrader (SERD) in Phase 2 clinical development for the treatment of ER+ HER2− breast cancer. Here we report data from Parts C and D of the ongoing Phase 1 study (SERENA-1) examining AZD9833 in combination with palbociclib, together with updated data from Parts A and B examining AZD9833 monotherapy. Methods: SERENA-1 (NCT03616587) is an ongoing open-label Phase 1 study of AZD9833 in pre- and post-menopausal women with ER+, HER2− advanced breast cancer who have previously received ≥1 endocrine therapy and ≤2 prior chemotherapies. Prior treatment with fulvestrant and/or CDK4/6 inhibitors was permitted. The…
Population Pharmacokinetics of Palbociclib in aReal-World Situation
2021
Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrat…
Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients
2021
Palbociclib is an oral CDK4/6 inhibitor indicated in HR+/HER2- advanced or metastatic breast cancer in combination with hormonotherapy. Its main toxicity is neutropenia. The aim of our study was to describe the kinetics of circulating neutrophils from real-life palbociclib-treated patients. A population pharmacokinetic (popPK) model was first constructed to describe palbociclib pharmacokinetic (PK). Individual PK parameters obtained were then used in the pharmacokinetic/pharmacodynamic (PK/PD) model to depict the relation between palbociclib concentrations and absolute neutrophil counts (ANC). The models were built with a population of 143 patients. Palbociclib samples were routinely collec…