Positive results of a study using circulating cell-free tumour DNA-based test as a means to predict therapeutic response to immunotherapy in multiple solid tumour types have been announced.

The paper, by lead author Dr Glen J Weiss et al, was published online in the journal Clinical Cancer Research.

Immunotherapy has become prominent in recent years as a result of remarkable response rates seen in previously unresponsive cancers and overall survival benefits seen in patients.

However, there are several issues with the approach.

First, only a minority of patients usually respond or have disease control with treatment.

Second, there can be serious adverse effects with immunotherapy, including an acceleration of cancer growth referred to as hyper-progression.

Third, immunotherapy is in general very expensive and consequently there is a high cost to healthcare payers given that many patients do not respond.

The publication describes a blinded, prospective study designed to validate an algorithm, based on changes in the assays proprietary genomic copy number instability (CNI) score, for predicting response to treatment after one or two cycles of immunotherapy in a range of cancers.

The study was conducted using blood samples from 56 patients with different tumour types including lung, kidney, breast, pancreatic, colorectal cancers and melanoma.

All patients were undergoing treatment with immunotherapy, mostly anti-PD1 immune checkpoint inhibitors with concurrent chemotherapy.

Three important points were observed in this study:

• The study showed the test provided an 83% overall prediction accuracy in predicting response and disease control/progression, with a positive predictive value for progression of 92% after one cycle of immunotherapy. After a second cycle of immunotherapy, the CNI-score yielded a 100% positive predictive value for progression.
• Six cases of hyper-progression were observed, five of which could be identified by CNI-score at a significantly earlier time point than by the current practice of imaging (six- nine weeks earlier).
• One patient with progressive disease who had been misclassified as stable on the basis of imaging assessments was able to be identified by the CNI score.

The Clinical Cancer Research paper is the first peer-reviewed publication describing the CNI-based approach with immunotherapy and may be the first for any therapeutic monitoring strategy based on a liquid biopsy with this class of drug.

The study demonstrates that CNI-based therapeutic monitoring test can identify progressing and hyper-progressive patients earlier than with currently available technologies.

This could allow treating physicians to switch progressing or hyper-progressive patients to alternative therapies sooner and achieve better treatment outcomes, as identifying these patients through imaging or other methods can take several months.

Furthermore, the fact the study showed accurate prediction of response and disease control with different cancers and with patients undergoing various treatments suggests the test should have broad applicability.

The paper’s lead author Dr Weiss commented “The key finding is the ability of the test to make an early prediction of response and disease control, just three to four weeks after initiation of immunotherapy. The flexibility to switch treatments early on based on an accurate prediction has great potential to improve the treatment of many cancers.”

An interim dataset from the study was presented at the American Society of Clinical Oncology Annual Meeting last year.

The blood test is produce by Chronix Biomedical Inc. 

Chronix Biomedical’s CEO, Dr Howard B. Urnovitz, commented “We are pleased to be able to share fully the details of this study with the oncology community, and highlight the performance of our CNI-based test, with the publication in Clinical Cancer Research. With advances occurring almost daily in the treatment of cancer with immunotherapy, we expect therapeutic monitoring of response to gain additional importance.”

Source: Businesswire