Search

ABSTRACT Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4′′- O-glucoside, vitexin-2′′- O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds an E3 ubiquitin ligase and ER to directly trigger ubiquitination of ER and its subsequent proteasomal degradation. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients with ER+/HER2- advanced breast cancer. The global, randomized Phase III VERITAC-2 study compares efficacy and safety of vepdegestrant versus fulvestrant in adults with ER+/HER2- advanced breast cancer after treatment with a CDK4/6 inhibitor plus endocrine therapy. Progression-free survival by blinded independent central review (primary end point) will be assessed in the intention-to-treat population and ESR1 mutation-positive subpopulation. Secondary end points include overall survival, tumor response, safety, pharmacokinetics, patient-reported outcomes, and circulating tumor DNA biomarkers. Clinical trial registration: NCT05654623 (ClinicalTrials.gov).

Aim: Palbociclib was approved in the United States in 2015 to treat estrogen receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This study evaluated outcomes and safety in patients treated with palbociclib in Australia and India with hormone receptor-positive (HR+)/HER2- ABC before palbociclib became commercially available., Methods: Postmenopausal women (≥18 years) with HR+/HER2- ABC who were appropriate candidates for letrozole therapy received palbociclib 125 mg once daily for 21 days followed by 7 days off, and letrozole 2.5 mg once daily (continuous). Safety, tumor response, and patient-reported outcomes (Australian cohort) were evaluated., Results: In total, 252 patients received palbociclib plus letrozole (Australia, n = 152; India, n = 100). More patients in the Australian versus Indian cohort had received prior chemotherapy (advanced/metastatic setting: 45.9% vs. 32.0%), endocrine therapy (advanced/metastatic setting: 63.2% vs. 54.3%), and advanced/metastatic therapies (61.8% vs. 31.0%). The most frequently reported all-grade palbociclib-related treatment-emergent adverse events were neutropenia (66.7%), fatigue (35.3%), and stomatitis (26.6%); grade 3/4 neutropenia was reported as palbociclib-related in 62.7% of patients. Febrile neutropenia was reported in six patients (2.4%). Eight patients (3.2%) discontinued because of an adverse event. The objective response rate was 19.4% (95% CI, 14.7%-24.9%) overall and 2.3% in Australian patients with ≥2 lines of prior therapy for metastatic disease. Patient-reported quality of life scores were maintained throughout the study., Conclusions: In an expanded access setting in Australia and India, palbociclib plus letrozole was well tolerated in patients with HR+/HER2- ABC, with a safety profile consistent with previous reports., (© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Purpose: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed., Patients and Methods: In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer-free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival., Results: Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial., Conclusion: At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor-positive breast cancer., Competing Interests: Michael GnantEmployment: Sandoz (I)Honoraria: Amgen, Novartis, AstraZeneca, LillyConsulting or Advisory Role: Daiichi Sankyo, Veracyte, Tolmar¸ LifeBrain, Lilly Amylou C. DueckPatents, Royalties, Other Intellectual Property: Royalties from licensing fees for a patient symptom questionnaire (MPN-SAF) Miguel MartinHonoraria: Roche/Genentech, Lilly, Pfizer, Novartis, Pierre FabreConsulting or Advisory Role: Roche/Genentech, Novartis, Pfizer, Lilly, AstraZeneca, Taiho Pharmaceutical, PharmaMarSpeakers' Bureau: Lilly/ImClone, Roche/Genentech, Pierre FabreResearch Funding: Novartis (Inst), Roche (Inst)¸ Puma Biotechnology (Inst)Other Relationship: Roche, Novartis Hal J. BursteinThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript. Richard GreilHonoraria: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, MSD¸ Sandoz, AbbVie, Gilead Sciences, Daiichi SankyoConsulting or Advisory Role: Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead Sciences, Daiichi SankyoResearch Funding: Celgene (Inst), Merck (Inst), Takeda (Inst), AstraZeneca (Inst), Novartis (Inst), Amgen (Inst), Bristol Myers Squibb (Inst), MSD (Inst), Sandoz (Inst), Gilead Sciences (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, Amgen, Janssen-Cilag, AstraZeneca, Novartis, MSD, Celgene, Gilead Sciences, Bristol Myers Squibb, AbbVie, Daiichi Sankyo Antonio C. WolffThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Ionis PharmaceuticalsPatents, Royalties, Other Intellectual Property: A.C.W. has been named as an inventor on one or more issued patents or pending patent applications related to methylation in breast cancer, has assigned his rights to JHU, and participates in a royalty sharing agreement with JHUOpen Payments Link: https://openpaymentsdata.cms.gov/physician/357301/summary Arlene ChanHonoraria: Novartis, LillyConsulting or Advisory Role: LillyResearch Funding: Eisai Eric P. WinerHonoraria: Genomic Health, Genentech/RocheConsulting or Advisory Role: Leap Therapeutics, Seattle Genetics, Jounce Therapeutics, GlaxoSmithKline, Carrick Therapeutics, Lilly, G1 Therapeutics, Syros Pharmaceuticals, Genentech/Roche, Gilead Sciences, Zymeworks, AthenexResearch Funding: Genentech (Inst)Other Relationship: InfiniteMD Georg PfeilerHonoraria: Amgen, Roche/Genentech, Pfizer¸ Lilly, AstraZeneca/Merck, AstraZeneca/Daiichi Sankyo, Novartis, UCB, Accord HealthcareConsulting or Advisory Role: Pfizer¸ Amgen¸ Lilly, Novartis, AstraZeneca/Merck, AstraZeneca/Daiichi Sankyo, UCB, Roche/GenentechSpeakers' Bureau: Roche/Genentech, Pfizer, Lilly, Novartis, UCB, AstraZeneca/Merck, AstraZeneca/Daiichi Sankyo, Accord Healthcare, Amgen, Accord HealthcareResearch Funding: Pfizer, Roche/GenentechTravel, Accommodations, Expenses: Novartis, Lilly, Roche/Genentech, Lilly, AstraZeneca/Daiichi Sankyo Kathy MillerThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Merck, Genentech/Roche, Athenex, AstraZeneca, Bristol Myers Squibb/CelgeneResearch Funding: Taiho Pharmaceutical (Inst), Novartis (Inst), Seattle Genetics (Inst), Pfizer (Inst), Astex Pharmaceuticals (Inst), British Biotech (Inst), CytomX Therapeutics (Inst), Alphamab (Inst) Marco ColleoniResearch Funding: Roche (Inst) Gabor RubovskyConsulting or Advisory Role: Pfizer, Novartis, Roche, Gilead SciencesTravel, Accommodations, Expenses: Amgen Judith M. BlissResearch Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Puma Biotechnology (Inst), Pfizer (Inst), Roche (Inst), GlaxoSmithKline/Novartis (Inst), Lilly (Inst), Janssen-Cilag (Inst), Clovis Oncology (Inst)Travel, Accommodations, Expenses: Pfizer Ingrid A. MayerConsulting or Advisory Role: Novartis, AstraZeneca, Lilly, Genentech, GlaxoSmithKline, Immunomedics, MacroGenics, Pfizer, AbbVie, Seattle Genetics, Puma Biotechnology, Cyclacel, Blueprint Medicines, SanofiResearch Funding: Novartis (Inst), Pfizer (Inst), Genentech (Inst) Christian SingerHonoraria: Novartis, AstraZeneca/MedImmune, Daiichi Sankyo Europe GmbHConsulting or Advisory Role: AstraZeneca/MedImmune, Daiichi-Sankyo, Gilead Sciences, Sanofi/Aventis, NovartisSpeakers' Bureau: Novartis, AstraZeneca/MedImmuneResearch Funding: Novartis, Sanofi, Myriad Genetics, Roche, AstraZeneca/MedImmuneTravel, Accommodations, Expenses: Roche, Novartis Zbigniew NoweckiTravel, Accommodations, Expenses: Roche/Genentech Olwen HahnLeadership: Via OncologyStock and Other Ownership Interests: Teleflex MedicalHonoraria: Cardinal Health (I)Consulting or Advisory Role: Pfizer, hmpglobal.comTravel, Accommodations, Expenses: Cardinal Health (I) Jacqui ThomsonHonoraria: MSD Oncology, Roche/Genentech Norman WolmarkOpen Payments Link: https://openpaymentsdata.cms.gov/physician/159597 Hope S. RugoHonoraria: Puma Biotechnology, MylanConsulting or Advisory Role: SamsungResearch Funding: MacroGenics (Inst), OBI Pharma (Inst), Eisai (Inst), Pfizer (Inst), Novartis (Inst), Lilly (Inst), Genentech (Inst), Merck (Inst), Immunomedics (Inst), Odonate Therapeutics (Inst), Daiichi Sankyo (Inst), Seattle Genetics (Inst), Sermonix Pharmaceuticals (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: Pfizer, Novartis, Mylan, AstraZeneca Spain, MerckOpen Payments Link: https://openpaymentsdata.cms.gov/summary Guenther G. StegerHonoraria: Pfizer, Lilly, Novartis, Roche, AstraZeneca/Daiichi Sankyo, Teva, Pfizer, Lilly, NovartisTravel, Accommodations, Expenses: Roche, Teva Blanca Hernando Fernández de AránguizHonoraria: GlaxoSmithKline, PharmaMar, Clovis OncologyTravel, Accommodations, Expenses: Pfizer, MSD Oncology, Roche Tufia C. HaddadResearch Funding: Takeda (Inst) Meritxell Bellet EzquerraConsulting or Advisory Role: Pfizer, Lilly, NovartisSpeakers' Bureau: Lilly, Pfizer, Novartis Hannes FohlerEmployment: Takeda (I)Research Funding: Pfizer (Inst) Otto MetzgerHonoraria: Grupo Oncoclinicas, RocheResearch Funding: Susan G. Komen for the Cure (Inst), Pfizer (Inst), Roche/Genentech (Inst), Eisai (Inst), Cascadian Therapeutics (Inst), AbbVie (Inst)Travel, Accommodations, Expenses: Grupo Oncoclinicas Anita Jallitsch-HalperResearch Funding: Pfizer (Inst) Kadine SolomonEmployment: Alliance Foundation TrialsStock and Other Ownership Interests: Pfizer, Merck, Moderna Therapeutics Céline SchurmansResearch Funding: Pfizer (Inst), Roche/Genentech (Inst), AstraZeneca (Inst), Novartis (Inst), Servier (Inst), Pfizer (Inst), Sanofi (Inst)Patents, Royalties, Other Intellectual Property: My organization receives royalties from Agendia Kathy P. TheallEmployment: PfizerStock and Other Ownership Interests: PfizerHonoraria: PfizerTravel, Accommodations, Expenses: Pfizer Dongrui R. LuEmployment: PfizerStock and Other Ownership Interests: Pfizer Kathleen TennerStock and Other Ownership Interests: Merck Christian FeslResearch Funding: Pfizer (Inst) Angela DeMicheleResearch Funding: Pfizer (Inst), Genentech (Inst), Calithera Biosciences (Inst), Novartis (Inst) Erica L. MayerConsulting or Advisory Role: Lilly, Novartis, AstraZeneca, Gilead SciencesResearch Funding: Pfizer (Inst)No other potential conflicts of interest were reported.