the liquid biopsy will help decide who should have chemotherapy and who should not – WWN

After surgical removal of the tumor,
in approximately one third of patients with colon cancer in stages three and two at high risk
a micro-metastatic disease remainswhich is radiologically invisible, but can be diagnosed with the liquid biopsyone new technology
capable of determining the presence of tumor DNA in the blood of the patient and repeatable over time, thus allowing the choice of therapy to be personalized for the individual. This was revealed by the PEGASUS clinical study, presented in Madrid at the annual congress of Esmo, the European Society of Medical Oncology. The results of PEGASUS, promoted by the Institute Foundation of Molecular Oncology (IFOM), also suggest that, in patients with negative liquid biopsyyou can opt for one less intense therapyreducing its toxicity without compromising its effectiveness.

Prevent relapses and avoid unnecessary toxicity

Approximately one in three patients with operable stage III colorectal cancer a risk of recurrence after surgery due to the presence of micro-metastases which unfortunately currently available radiological techniques fail to detect – explains Silvia Marsoni, head of the Precision Oncology Unit at IFOM, creator and coordinator of the PEGASUS study -. To prevent recurrence, almost all patients today undergo chemotherapy after surgery. Not everyone benefits from this strategy and, above all, even patients who do not need it are treated because, until now, an adequate tool to measure residual microscopic disease was not available. This is one of the first prospective studies of liquid biopsy, a new technology capable of detecting the presence of circulating tumor DNA (ctDNA) in the blood of patients after surgery. The objective was therefore to test the feasibility of using this method to follow the course of the disease and guide therapeutic choices.

The experimentation, PEGASUS study

Between July 2020 and July 2022, 135 patients were recruited from 11 Italian and Spanish cancer centers. There post-surgical liquid biopsy tested positive in 35 patients out of 135 (26%), of which 12 (34%) had a recurrence, while only in 10% of the remaining 100 patients with a negative liquid biopsy, the disease recurred. The data on the negativity of liquid biopsy parameters during and at the end of all treatments administered as part of the protocol suggest an overall effectiveness of the therapy of 40%.
The PEGASUS study involves a differentiated post-surgical chemotherapy treatment based on the results of a liquid biopsy taken approximately four weeks after the surgical removal of the primary tumor – explains the clinical director of the study Sara Lonardi, of the Veneto Oncology Institute IRCCS in Padua, who illustrated the trial in Madrid –. With positive liquid biopsypatients receive a standard adjuvant chemotherapy (the same one used today for the treatment of all high-risk stage III and stage II colon cancers): the so-called CAPOX, i.e. a regimen based on capecitabine and oxaliplatin which is very active against colon cancer, but which can cause acute and chronic neurological toxicity in a substantial percentage of cases. With negative liquid biopsyinstead, patients receive a lighter therapy which involves the administration of capecitabine alone for precautionary purposes. The analysis of the liquid biopsy is carried out several times during the treatment and subsequently during the patient’s follow-up, as a tool to reveal any innate resistance of the tumor to therapy and guide the remodulation of the chemotherapy regimen and the use of a more aggressive treatment based on FOLFIRI.

Confirmations and new perspectives

The study, supported by the AIRC Foundation, saw the participation of 11 centers of oncology excellence under the scientific supervision of Salvatore Siena of the Department of Oncology and Hemato-oncology of the University of Milan and Grande Ospedale Metropolitano Niguarda and of Josep Tabernero, director of the Vall d’Hebron Institute of Oncology in Barcelona.If these results they will be confirmed from those of the various ongoing international studies which also include a direct comparison with standard therapy, will be able to contribute on one side to change the guidelines for the treatment of operable colon cancerreducing or completely eliminating adjuvant therapy in patients with negative liquid biopsy, and on the other hand a personalize chemotherapy in the event of a lack of molecular response – concludes Marsoni –. an important contribution to changing the paradigm with a new personalized therapy which will also allow explore the biology of micro-metastatic tumorsthose for whom we owe find new and more effective therapies.