Publications by authors named "Taran T"
Article Synopsis
- A study analyzed paired baseline and end-of-treatment circulating tumor DNA (ctDNA) samples from the MONALEESA trials to identify genetic changes in patients with HR+/HER2- advanced breast cancer treated with ribociclib plus endocrine therapy (ET) or a placebo.
- The analysis included 523 samples, revealing 21 genes with significant alterations at end-of-treatment, particularly highlighting increased mutations in RB1 and SPEN in the ribociclib group, while ESR1 mutations were noted in both treatment arms.
- The findings suggest acquired genetic alterations related to treatment response and resistance, providing insights for future research on resistance mechanisms and potential systemic therapies following CDK4/6 inhibitors.
Background: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.
Methods: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.
Background: The phase III MONALEESA trials tested the efficacy and safety of the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib with different endocrine therapy partners as first- or second-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Using the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date, we identified potential biomarkers of response to ribociclib.
Patients And Methods: Baseline circulating tumour DNA from patients in the MONALEESA trials was assessed using next-generation sequencing.
Article Synopsis
- Ribociclib has been shown to improve overall survival for patients with HR+/HER2- advanced breast cancer, and the NATALEE trial aims to evaluate its safety and effectiveness when combined with endocrine therapy for early nonmetastatic cases.* -
- This Phase III trial involves a randomized, multicenter design, enrolling men and women with specific stages of breast cancer, and compares ribociclib with endocrine therapy alone, focusing on invasive disease-free survival as the main outcome.* -
- The trial extends ribociclib treatment to 36 months to enhance effectiveness and uses a lower dosage to improve tolerability, including a diverse patient population for more comprehensive results on adjuvant therapy.*
Article Synopsis
- * After a median follow-up of 6.6 years, results showed that patients receiving ribociclib had a median overall survival of 63.9 months compared to 51.4 months for those on placebo, indicating a significant survival benefit.
- * The research concluded that first-line treatment with ribociclib plus letrozole significantly improves overall survival without introducing new safety concerns, with an overall survival increase of over 12 months.
Purpose: This analysis evaluated the genomic landscape of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and the association of genetic alterations with response to ribociclib in the phase III MONALEESA-7 trial.
Methods: Premenopausal patients were randomly assigned 1:1 to receive endocrine therapy plus ribociclib or placebo. Plasma collected at baseline was sequenced using targeted next-generation sequencing for approximately 600 relevant cancer genes.
Background: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months).
View Article and Find Full Text PDFPurpose: The prognostic and predictive value of intrinsic subtypes in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with endocrine therapy and ribociclib (RIB) is currently unknown. We evaluated the association of intrinsic subtypes with progression-free survival (PFS) in the MONALEESA trials.
Methods: A retrospective and exploratory PAM50-based analysis of tumor samples from the phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials was undertaken.
As the interest in genetic resequencing increases, so does the need for effective mathematical, computational, and statistical approaches. One of the difficult problems in genome annotation is determination of precise positions of transcription start sites. In this paper, we present TransPrise-an efficient deep learning tool for predicting positions of eukaryotic transcription start sites.
View Article and Find Full Text PDFBackground: In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival.
Methods: Patients were randomly assigned in a 2:1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment.
Background: An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival.
Methods: We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen).
Purpose Of Review: We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children's Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland).
Recent Findings: Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma. Subsequent approvals in the European Union, Switzerland, and Canada soon followed.
Purpose: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).
Patients And Methods: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).
Results: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders ( = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( = 8; 74% and 104% higher geometric mean Cmax and AUC0-28d, respectively) with persistence measurable beyond 2 years in responding patients.
Importance: Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer.
Objective: A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.
Design: Open-label, randomized, phase 2 trial of treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors.
Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival.
View Article and Find Full Text PDFBackground: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Methods: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months.
As part of the SAMPL5 blinded experiment, we computed the absolute binding free energies of 22 host-guest complexes employing a novel approach based on the BEDAM single-decoupling alchemical free energy protocol with parallel replica exchange conformational sampling and the AGBNP2 implicit solvation model specifically customized to treat the effect of water displacement as modeled by the Hydration Site Analysis method with explicit solvation. Initial predictions were affected by the lack of treatment of ionic charge screening, which is very significant for these highly charged hosts, and resulted in poor relative ranking of negatively versus positively charged guests. Binding free energies obtained with Debye-Hückel treatment of salt effects were in good agreement with experimental measurements.
View Article and Find Full Text PDFThe problems of catering control various client groups during the XXII Olympic Winter Games and XI Paralympic Winter Games of 2014 in Sochi is one of the priorities of the sanitary and epidemiological welfare of the population during mass events. The data on the order of nutrition of guests and participants of the games, control of food items, sanitary and microbiological monitoring of drinking water, food raw materials and products are presented. It is noted that the ongoing supervisory activities contributed to the sanitary and epidemiological well-being during the Games.
View Article and Find Full Text PDFPurpose: Two recent phase III trials, BOLERO-1 and BOLERO-3 (Breast Cancer Trials of Oral Everolimus), evaluated the addition of everolimus to trastuzumab and chemotherapy in human epidermal growth factor receptor 2-overexpressing advanced breast cancer. The current analysis aimed to identify biomarkers to predict the clinical efficacy of everolimus treatment.
Methods: Archival tumor samples from patients in BOLERO-1 and BOLERO-3 were analyzed using next-generation sequencing, immunohistochemistry, and Sanger sequencing.
Purpose: To explore the genetic landscape of tumors from patients enrolled on the BOLERO-2 trial to identify potential correlations between genetic alterations and efficacy of everolimus treatment. The BOLERO-2 trial has previously demonstrated that the addition of everolimus to exemestane prolonged progression-free survival by more than twofold in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer previously treated with nonsteroidal aromatase inhibitors.
Patients And Methods: Next-generation sequencing was used to analyze genetic status of cancer-related genes in 302 archival tumor specimens from patients representative of the BOLERO-2 study population.
There is presented the analysis of activities of the Federal Service for Supervision of Consumer Rights protection and Human Welfare to ensure adequate conditions of accommodation of the participants, attendants and guests of the XXII Olympic Winter Games and XI Paralympic Winter Games of 2014 in the Resort city of Sochi according to regulated requirements. There were detected ways of the strengthening the supervision for the quality of the accommodation during mass sports activities for the assurance of the rights for consumers.
View Article and Find Full Text PDFBackground: mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss, by sensitising PTEN-deficient tumours to trastuzumab. The BOLERO-1 study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer.
Methods: In this phase 3, randomised, double-blind trial, patients were enrolled across 141 sites in 28 countries.