Search Our Scientific Publications & Authors

Publications
find publications by category +
Translate page:

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer.

Authors:
Matthew J Wongchenko Sung-Bae Kim Cristina Saura Mafalda Oliveira Doron Lipson Mark Kennedy Mandy Greene Virginia Breese Aruna Mani Na Xu Rebecca Dent

JCO Precis Oncol 2020 Nov;4:1012-1024

Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.

Purpose: Combining the oral AKT inhibitor ipatasertib with paclitaxel as first-line therapy for metastatic triple-negative breast cancer significantly improved progression-free survival (PFS) in the placebo-controlled, randomized, phase II LOTUS trial, with a more pronounced effect in patients with -altered tumors. We report findings from the extensive translational research program.

Patients And Methods: Pretreatment plasma and tumor samples were evaluated for genetic alterations using FoundationACT and FoundationOne (Foundation Medicine, Cambridge, MA) hybrid capture next-generation sequencing assays, respectively. Prevalences of the most common mutations and mutation status were determined using both assays, and concordance was assessed. In longitudinal analyses, circulating tumor DNA (ctDNA) mutations were quantified in baseline and on-treatment (cycle 3, day 1 [C3D1]) samples. The relationship between outcomes and ctDNA fraction (CTF; highest variant allele frequency) and CTF ratio (C3D1 CTF to baseline CTF) was explored.

Results: Among 89 patients evaluable for ctDNA sequencing, 81 patients (91%) had 149 detectable mutations. There was high agreement between plasma- and tissue-based sequencing for known or likely short variant mutations but not amplifications. There was 100% concordance between ctDNA and tissue sequencing in patients with activating or mutations. High baseline CTF was associated with shorter PFS in both treatment arms. Longitudinal analyses showed more favorable outcomes with lower absolute CTF at C3D1 and, to a lesser extent, greater CTF decreases.

Conclusion: These results suggest that plasma ctDNA sequencing may allow reliable and convenient assessment of prognosis and identification of genetic markers associated with increased benefit from ipatasertib. On-treatment CTF showed a meaningful association with objective response and PFS.

Download full-text PDF

 Source
http://dx.doi.org/10.1200/PO.19.00396DOI Listing
November 2020

Publication Analysis

Top Keywords

mutations high
8
baseline ctf
8
longitudinal analyses
8
sequencing patients
8
circulating tumor
8
ctdna sequencing
8
breast cancer
8
triple-negative breast
8
ipatasertib paclitaxel
8
metastatic triple-negative
8
tumor dna
8
ctf
8
ctdna
5
mutations
5
sequencing
5
next-generation sequencing
4
evaluated genetic
4
tissue-based sequencing
4
sequencing assays
4
plasma- tissue-based
4

Keyword Occurance

Similar Publications

Diagnostic Dilemma of Hemoglobinopathies Using High Performance Liquid Chromatography Alone: A Case Report from a Resource-Constrained Setting.

Authors:
Ankita Sen Aditi Sen Tuphan Kanti Dolai

Hemoglobin 2022 May 16:1-4. Epub 2022 May 16.

Department of Haematology, Nil Ratan Sircar Medical College and Hospital, Sealdah, Kolkata, West Bengal, India.

Hemoglobinopathies are quite common in India, and multiple awareness and screening initiatives exist for detection of thalassemia in the population. One of the most common and successfully used method for thalassemia screening is the high performance liquid chromatography (HPLC) test. However, in spite of its excellent usefulness as a screening tool, there are situations where HPLC alone may not be able to make an accurate diagnosis. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

Aqueous humor as a surrogate biomarker for retinoblastoma tumor tissue.

Authors:
Vishal Raval Hilary Racher Jacquelyn Wrenn Arun D Singh

J AAPOS 2022 May 13. Epub 2022 May 13.

Department of Ocular Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: To demonstrate the feasibility of identifying a germline RB1 pathogenic variant in retinoblastoma (RB) from an aqueous humor (AH) sample.

Methods: In this pilot case series, peripheral blood, fresh tumor tissue, and AH were obtained from 3 eyes of 3 RB patients who underwent enucleation at a tertiary eye care institute. After isolation of the cell-free DNA (cfDNA), sequence analysis of the RB1 core promoter and of exons 1 through 27, including nearby flanking intronic regions, was performed using a custom targeted hybridization protocol, followed by high-throughput sequencing. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

Gliomas: Genetic alterations, mechanisms of metastasis, recurrence, drug resistance, and recent trends in molecular therapeutic options.

Authors:
Siddarth Kannan Avaniyapuram Kannan Murugan Sathyamoorthy Balasubramaniam Arasambattu Kannan Munirajan Ali S Alzahrani

Biochem Pharmacol 2022 May 13:115090. Epub 2022 May 13.

Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh - 11211 Saudi Arabia; Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh - 11211 Saudi Arabia.

Glioma is the most common intracranial tumor with poor treatment outcomes and has high morbidity and mortality. Various studies on genomic analyses of glioma found a variety of deregulated genes with somatic mutations including TERT, TP53, IDH1, ATRX, TTN, etc. The genetic alterations in the key genes have been demonstrated to play a crucial role in gliomagenesis by modulating important signaling pathways that alter the fundamental intracellular functions such as DNA damage and repair, cell proliferation, metabolism, growth, wound healing, motility, etc. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study.

Authors:
Naveen Pemmaraju Jacqueline S Garcia Jalaja Potluri Jason G Harb Yan Sun Paul Jung Qin Q Qin Srinivas K Tantravahi Srdan Verstovsek Claire Harrison

Lancet Haematol 2022 May 13. Epub 2022 May 13.

Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address:

Background: Primary analyses of cohort 1a of the REFINE trial showed that addition of navitoclax to ruxolitinib induced a 35% or greater reduction in spleen volume (SVR) and reduced symptoms in patients with myelofibrosis no longer benefiting from ruxolitinib. Here, we report the exploratory post-hoc biomarker analyses from cohort 1a.

Methods: REFINE is a phase 2, multicentre, open-label trial designed to assess the activity and safety of navitoclax alone or in combination with ruxolitinib in patients with primary or secondary (post-polycythaemia vera or post-essential thrombocythaemia) myelofibrosis. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

High DDT resistance without apparent association to kdr and Glutathione-S-transferase (GST) gene mutations in Aedes aegypti population at hotel compounds in Zanzibar.

Authors:
Ayubo Kampango Emma F Hocke Helle Hansson Peter Furu Khamis A Haji Jean-Philippe David Flemming Konradsen Fatma Saleh Christopher W Weldon Karin L Schiøler Michael Alifrangis

PLoS Negl Trop Dis 2022 May 16;16(5):e0010355. Epub 2022 May 16.

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Global efforts to control Aedes mosquito-transmitted pathogens still rely heavily on insecticides. However, available information on vector resistance is mainly restricted to mosquito populations located in residential and public areas, whereas commercial settings, such as hotels are overlooked. This may obscure the real magnitude of the insecticide resistance problem and lead to ineffective vector control and resistance management. Read More

View Article and Full-Text PDF
May 2022
Similar Publications
}