Medicilon Logo
search icon search icon language icon contact icon menu icon
Medicilon Logo
search icon close search icon language icon contact icon menu icon
Contact Us
Close Button
Back To Top
Online Message×
Click switch
Close Button
Medicilon's News information
News information

Immunotherapy Response Predicted by Liquid Biopsy

Page View:

Mutations in circulating tumor DNA (ctDNA) may indicate which patients are likely to respond to checkpoint inhibition, according to research published in Clinical Cancer Research.


“We can help predict response to immunotherapy by measuring the number of mutations in circulating tumor DNA [ctDNA] using a simple blood test,” said Yulian Khagi, M.D., University of California San Diego Moores Cancer Center fellow and first author. “Immunotherapy can result in serious side effects, and therefore being able to predict who will respond is important to mitigating potential risk to each patient.”


The team’s study (“Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor–Based Immunotherapy”), published in Clinical Cancer Research, demonstrates that 45% of patients with more than three genomic alterations detected in ctDNA responded to checkpoint inhibitor-based immunotherapy. Patients with fewer alterations had a 15% response.


“We assessed 69 patients with diverse malignancies who received checkpoint inhibitor–based immunotherapy and blood-derived ctDNA NGS testing (54–70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations. Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively; P = 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs.<6). statistically="" significant="" os="" improvement="" was="" also="" associated="" with="" high="" vus="" alteration="" status.="" two-month="" landmark="" analysis="" showed="" that="" responders="" versus="" nonresponders="">3 had a median PFS of 23 versus 2.3 months (P = 0.0004),” wrote the investigators.

“Given the association of alteration number on liquid biopsy and checkpoint inhibitor–based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted.”


“Checkpoint inhibitor immunotherapy is exciting, but it is currently given to patients with all types of cancer, and most of the time it is not known if it will result in a response,” said Razelle Kurzrock, M.D., director of the Center for Personalized Cancer Therapy at UC San Diego Moores Cancer Center and senior author of the study. “Indeed, more than 80% of patients with cancer fail to respond to checkpoint inhibitor immunotherapy.”


Patients with a high number of alterations also had longer PFS. Those who responded to immunotherapy at two months and had high numbers of genomic alterations in the blood had a median response last nearly two years.


“Considering that many of these patients had advanced disease that was resistant to many other therapies, this result is impressive,” said Dr. Kurzrock, who added that although findings mirror what have been previously described in genomic testing of tissue samples, the results in this study were obtained from a small tube of blood without a tissue biopsy.


Once reactivated with the use of checkpoint inhibitor immunotherapy, the immune system needs to recognize cancer cells. The more mutations a cancer cell harbors, the more it stands out compared to normal tissue, and the easier it is for the immune system to recognize and target a tumor, he explained.


“Tumor that have the most mutations, and used to be considered the worst tumors, are now considered the best cancers in that they are the most amenable to treatment with immunotherapy,” noted Dr. Kurzrock, who said the researchers used the Guardant360® liquid biopsy assay, which evaluated up to 70 genes for genomic alterations.


Dr. Kurzrock is already using liquid biopsy technology in the Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT) clinical trial, a project focusing on the outcome of patients who have genomic testing performed on their tumors and are treated with targeted therapy.


The team says larger studies are required to corroborate that blood-based liquid biopsy can be used as a viable, noninvasive, predictive biomarker for response to checkpoint inhibitor-based immunotherapy across a variety of cancers.

Relevant newsRelevant news