A5061176953- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer-related Molecular Pathways
- Lung Cancer Research Studies
- Breast Cancer Treatment Studies
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- Neuroendocrine Tumor Research Advances
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Pancreatic and Hepatic Oncology Research
- Renal and related cancers
- 14-3-3 protein interactions
- Plant biochemistry and biosynthesis
- Gastrointestinal Tumor Research and Treatment
- Botanical Studies and Applications
- Colorectal Cancer Treatments and Studies
- Gastric Cancer Management and Outcomes
- Monoclonal and Polyclonal Antibodies Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Neuroblastoma Research and Treatments
- Cancer-related cognitive impairment studies
- Male Breast Health Studies
- Organoboron and organosilicon chemistry
Pfizer (United States)
2016-2025
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
2025
Pfizer (United Kingdom)
2024
Wenzhou Medical University
2024
First Affiliated Hospital of Wenzhou Medical University
2024
Sichuan University of Science and Engineering
2024
Centre Eugène Marquis
2018
Ludwig-Maximilians-Universität München
2018
Pfizer (Spain)
2018
University of California, San Francisco
2018
The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 2 trials.
A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than alone in the initial treatment of postmenopausal women estrogen-receptor (ER)–positive, human epidermal growth factor receptor (HER2)–negative advanced breast cancer. We performed a 3 designed to confirm and expand efficacy safety data for this indication.
BackgroundHypertension (HTN) is an on-target effect of the vascular endothelial growth factor pathway inhibitor, sunitinib. We evaluated association sunitinib-induced HTN with antitumor efficacy and HTN-associated adverse events in patients metastatic renal cell carcinoma.
This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib.In total, 512 were randomly assigned 1:1 to receive intravenous 25 mg once weekly (n = 259) or oral 400 twice per day 253),...
In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups extended follow-up. this double-blind, phase 3 study, post-menopausal ER+/HER2− ABC who had not received prior...
Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, potential value of adding palbociclib to endocrine therapy hormone receptor-positive cancer has not been confirmed.
LBA1003 Background: PAL was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved for ER+/HER2– ABC based on randomized, phase 2 PALOMA-1 study. PALOMA-2 is a double-blind, 3 trial in first-line that confirmed clinically and statistically significant improvement progression-free survival (PFS) with PAL+LET versus PBO+LET (median PFS, 27.6 vs 14.5 months; hazard ratio, 0.56 [95% CI, 0.46–0.69]; P<0.0001). At time of final PFS analysis, OS data were not mature. Herein, we report...
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary point, may be published when key planned coprimary or secondary analyses are not yet available. trial updates provide an opportunity to disseminate additional results from studies, in JCO elsewhere, for which point has already been reported. PALOMA-2 demonstrated statistically and clinically significant improvement progression-free survival with...
Purpose. This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. Experimental design. Patients 50 mg/day on Schedule 4/2 (4 weeks treatment, followed by 2 off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival...
<h2>Abstract</h2><h3>Background</h3> Patient-reported outcomes are integral in benefit–risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body evidence for patient-reported health-related quality life (QOL) patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and alone). <h3>Patients methods</h3> Treatment-naïve postmenopausal women estrogen receptor-positive (ER+)/human epidermal growth factor...
507 Background: Hormonal therapy (HT) is the mainstay for patients (pts) with ER+ BC. P, a cyclin-dependent kinase 4/6 inhibitor, blocks growth of ER+/HER2– BC preclinical models. In PALOMA-1, an open-label Ph 2 trial, addition P to L improved median PFS vs alone (20.2 months [mo] 10.2 mo) in pts first-line ABC acceptable safety, leading accelerated FDA approval. PALOMA-2 randomized double-blind 3 trial designed confirm these results. Methods: 666 postmenopausal no prior systemic were 2:1...
BackgroundThis report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) or without visceral metastases.Patients methodsPre- postmenopausal disease progression following prior ET (PALOMA-3; N= 521) untreated for ABC (PALOMA-2; 666) were randomized 2:1 to (fulvestrant letrozole, respectively) placebo. Progression-free survival (PFS), safety,...
TPS1122 Background: ARV-471 is an oral PROTAC ER degrader that binds to and degrades wild-type clinically relevant mutants. directly recruits the ubiquitin-proteasome system degrade ER, whereas selective degraders (SERDs) indirectly cause degradation. In a first-in-human phase 1/2 study, monotherapy was well tolerated showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The 3 dose (200 mg once daily [QD]) chosen due comparable efficacy favorable...
Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds E3 ubiquitin ligase and to directly trigger ubiquitination of its subsequent proteasomal degradation. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients ER+/HER2- advanced breast cancer. The global, randomized III VERITAC-2 study compares efficacy safety versus fulvestrant adults cancer after treatment CDK4/6 inhibitor plus endocrine therapy....
Palbociclib administered with endocrine therapy was tolerable when the overall incidence of toxicities assessed separately for three PALOMA studies. This study analyzed pooled, longer-term safety data longitudinally.Data were pooled from randomized phase II and III studies (ClinicalTrials.gov: NCT00721409, NCT01740427, NCT01942135) hormone receptor-positive/human epidermal growth factor receptor 2‒negative advanced breast cancer patients. Front-line patients randomly assigned to receive...
In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed the benefit in Asians.
PALOMA-2 confirmed that first-line palbociclib + letrozole improved progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.46-0.72) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This analysis evaluated palbociclib-associated hematologic adverse events (AEs) and provides insight on managing these AEs.Postmenopausal ER+/HER2- ABC were randomly assigned 2:1 to (2.5 mg daily...
Previous studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer treatment exposure.Data were pooled from three randomized patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic for disease (PALOMA-1/-2) pre- progressed ET (PALOMA-3).Updated...
PURPOSE The PALLAS study investigated whether the addition of palbociclib, an oral CDK4/6 inhibitor, to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer. In this analysis, we evaluated palbociclib exposure and discontinuation PALLAS. METHODS Patients with stage II-III HR+, HER2– disease were randomly assigned 2 years ET versus alone. primary...