Αρχική World News Potential Clinical Utility of ctDNA-based Surveillance in Patients Treated with ICI

Potential Clinical Utility of ctDNA-based Surveillance in Patients Treated with ICI

Findings from the INSPIRE, a prospective phase II clinical trial to assess circulating tumour DNA (ctDNA) in five cohorts of patients with advanced solid tumours treated with pembrolizumab, demonstrate the potential for broad clinical utility of ctDNA-based surveillance in patients treated with immune checkpoint inhibitors (ICIs). Lillian L. Siu and Trevor J. Pugh of the Princess Margaret Cancer Centre, University Health Network in Toronto, Ontario, Canada and colleagues reported the results from this investigator-initiated study of pembrolizumab immunological response evaluation on 6 August 2020 in the Nature Cancer.

Less than 20% of patients treated with anti-PD1/PD-L1 respond to treatment or have durable clinical benefit. Numerous classes of biomarkers have been proposed, but there is no robust predictive marker of treatment response. Early determination of response to immune checkpoint inhibitors (ICIs) could enable patients who are deriving clinical benefit to continue therapy, while sparing others from unnecessary toxicities and cost.

Standard radiologic criteria for response to ICIs do not consistently capture the dynamics of clinical benefit over time. Furthermore, repeated tumour biopsies are usually not feasible, may be difficult to time appropriately, and may not add meaningful predictive information early in the treatment course. This forms a strong rationale to pursue new non-invasive biomarkers of ICI response that can provide predictive value and/or early determination of clinical benefit.

ctDNA within peripheral blood plasma provides non-invasive access to cancer-specific somatic mutations. This class of biomarkers is poised to revolutionise the management of patients with advanced cancer by replacing tissue biopsy for non-invasive genotyping of specific mutations that are linked with therapeutic response.

Despite its potential, ctDNA has not yet been clinically implemented for patients treated with ICIs. Proof-of-principle studies suggest that ctDNA quantification and on-treatment changes could assist in prognostication and response monitoring, but the robustness of these findings have been limited by small cohort sizes, heterogeneous treatment regimens and variable ctDNA detection methodologies.

In their article, the authors present the results of a prospective clinical trial of ICI in distinct cohorts of advanced solid tumours. They evaluated the performance of an amplicon-based bespoke ctDNA detection platform for prognostication and response monitoring in patients treated with the anti-PD-1 monoclonal antibody, pembrolizumab. They hypothesized that baseline ctDNA levels would be prognostic and early changes in ctDNA levels would precede radiographic response.

The study team conducted a prospective, single-institution phase II study to assess ctDNA in patients with advanced solid tumours treated with pembrolizumab (NCT02644369). They included patients in 5 parallel cohorts with squamous cell cancer of head and neck, triple negative breast cancer, high-grade serous ovarian cancer, melanoma and mixed solid tumours.

The study investigators applied bespoke ctDNA assays to 316 serial plasma samples obtained at baseline and every three cycles from 94 patients. Baseline ctDNA concentration correlated with progression-free survival, overall survival, clinical response and clinical benefit. This association became stronger when considering ctDNA kinetics during treatment. All 12 patients with ctDNA clearance during treatment were alive with median 25 months follow-up.

The study investigators concluded that their study demonstrates the potential for broad clinical utility of ctDNA-based surveillance in patients treated with ICI. Their findings could help advance the implementation of ctDNA-based testing in the context of ICI treatment across cancer types.

Anonymized WES data of tumour and match normals are available with controlled access approval through the European Genome-Phenome Archive under accession number EGAS00001003280.  

Major funding support for this project was made possible by the Princess Margaret Cancer Foundation, Ontario Institute for Cancer Research and Terry Fox Research Institute. Merck contributed the study drug for the clinical trial. 

Reference

Bratman SV, Yang YC, Iafolla MAJ, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer; Published online 6 August 2020. DOI: https://doi.org/10.1038/s43018-020-0096-5

Source

NEWSLETTER

Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like
57ΑκόλουθοιΑκολουθήστε

Διαβαστε Επίσης

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ)

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...

Καρκίνος: Ευεργετική για τους καρκινοπαθείς η άσκηση

Σημαντικά ωφέλη προσφέρει η άσκηση, ακόμη και σε ασθενείς με καρκίνο. Οι περισσότεροι ασθενείς αγνοούν τα οφέλη που μπορεί να έχει γι’ αυτούς η συχνή...

Prostate Cancer

The article is provided by Scientific Communications Officer of NIPD Genetics, Ms Marina Charitou (MSc) Prostate Cancer Awareness Prostate cancer is the second most common cancer...
- Advertisment -

Ροή Ειδήσεων

EMA Recommends Granting a Marketing Authorisation for Lenalidomide Mylan

On 15 October 2020, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting...

Easy Meals at Home

Our theme this week is delicious, easy to make, at home meals. These recipes minimize your cook time and maximize your food enjoyment. Ingredients 8...

This Saturday: National Prescription Drug Take-Back Day

Have you taken a look at your medicine cabinet lately? Aside from cotton swabs, mouthwash and makeup remover, are there old, outdated prescription drugs...

How People With Cancer Can Benefit From Online Therapy

Tanya J. Peterson, MS, is credentialed with the National Board of Certified Counselors. She is a regular contributor to the mental health website, Choosing...

EMA Recommends Granting a Conditional Marketing Authorisation for Autologous Anti-CD19-Transduced CD3+ Cells

On 15 October 2020, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting...

New Treatment Helps Survivors Regain Sensation After Breast Cancer

When NBC’s Kristen Dahlgren was diagnosed with breast cancer, she didn’t think much about the lack of sensation that her mastectomy would likely leave...