Guardant Health, a precision oncology company, announced that initial results from the PEGASUS trial suggest liquid biopsy may be used in post-surgical clinical management to reduce unnecessary toxicity from chemotherapy and improve the response to standard chemotherapy regimens in patients with stage III or high-risk stage II colon cancer.

Results from the trial, which is an ISS study sponsored by IFOM ETS – the AIRC Institute of Molecular Oncology in Milan, Italy, and supported by Guardant Health, were presented by study investigators at the ESMO Congress in Madrid, Spain.

One of the first prospective studies using liquid biopsy, the PEGASUS trial includes 135 patients recruited from 11 cancer centers in Italy and Spain. The study is assessing the feasibility of escalating or de-escalating adjuvant (post-surgery) chemotherapy based on the presence or absence of minimal residual disease (MRD) as indicated by circulating tumor DNA (ctDNA) detected by the Guardant Reveal blood test at multiple timepoints. 

Patients with positive results receive standard chemotherapy, while patients with negative results receive a milder therapy that is associated with significantly less acute and chronic neurological toxicity compared to standard treatment. Liquid biopsy is repeated several times along the course of treatment to reveal opportunities to treat patients safely with lower toxicity regimens, identify therapeutic resistance, and tailor chemotherapy to be stronger when needed.

Further reading: Guardant Health and Ohio State University to Study Colon Cancer Screening Adherence

Initial results show that 34% of patients with a positive liquid biopsy result after surgery had the cancer return, while only 10% of patients with a negative result experienced a relapse. Approximately 40% of patients converted from ctDNA-positive to ctDNA-negative after treatment, suggesting treatment efficacy of chemotherapy for some patients.

“We are confident that, once confirmed by the results of several other ongoing international studies on liquid biopsy, our findings may help influence the modification of clinical practice guidelines for the treatment of operable colon cancer, supporting adjuvant therapy scale-down or elimination in patients with negative liquid biopsy, and chemotherapy personalization in the case of molecular non-response,” says Silvia Marsoni, MD, PhD, the designer of the PEGASUS trial and head of the precision oncology unit at IFOM. “A shift from the current paradigm of one-size-fits-all chemotherapy toward a new paradigm of tailored therapies is not the only expected impact of the PEGASUS trial. It will allow us to explore the biology of micro-metastatic tumors, for which we need to find new and more effective therapies.”

“Currently a significant number of patients with stage II and III colon cancer do not receive the intended benefit from adjuvant chemotherapy due to limits of current prognostic criteria. There is a significant need for better prognostic tools to guide clinical management in this patient population,” says Craig Eagle, MD, Guardant Health chief medical officer. “These initial trial results are promising and suggest that the Guardant Reveal liquid biopsy test can provide a sensitive tool to detect MRD and predict recurrence of the cancer, helping oncologists make informed treatment decisions that improve outcomes for their patients.”