In patients with colon cancer, liquid biopsy can improve surgical outcomes and help personalize treatment. The first data from the Pegasus study indicate this: in patients with a negative liquid biopsy, it was possible to choose a lighter and less toxic therapy than chemotherapy, without compromising the prognosis. With these results, presented at the European Society of Medical Oncology (Esmo) congress, the study marks an important step forward for precision oncology in the treatment of these tumors.
Micrometastases invisible to x-rays and the reasons for Pegasus
About one in 3 patients with colon operable tumors at the III stadium after surgery is at risk of recurrence due to the presence of micro-metastases that current radiological techniques are unable to detect. “To prevent recurrence today almost all patients after intervention are subjected to adjuvant chemotherapy,” he explains Silvia Marsoni director of the Precision Oncology unit of the Ifom – ETS Institute of Molecular Oncology Foundation in Milan, creator and coordinator of Pegasus. But “since medicine does not yet have an adequate tool available to measure residual micro-metastatic disease – she adds – not all patients benefit from adjuvant treatment. Above all, even those who don’t need it are treated.”
The Pegasus studio
Liquid biopsy can be used (today still in an experimental setting) to monitor circulating tumor DNA (ctDNA) in the blood over time, and verify both its presence after surgery and the response of the disease to treatment. Promoted by Ifom and supported by the Airc Foundation, between July 2020 and July 2022, in the midst of the pandemic, Pegasus recruited 135 patients being treated in 11 Italian and Spanish oncology centers of excellence. The post-surgical liquid biopsy was positive (i.e. there was tumor DNA in the blood) in 35 out of 135 patients (26%): 12 of them (34%) had a recurrence. However, the disease recurred only in 10% of patients with a negative liquid biopsy (i.e. without tumor DNA in the blood). The data on the negativity of liquid biopsy parameters during and at the end of all treatments suggest an overall effectiveness of the therapy of approximately 40%.
by Tina Simoniello
“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 – he explains Sara Lonardi, of the Veneto IRCCS Oncological Institute of Padua (one of the centers involved in the project), clinical manager of the study that presented the results at the Madrid conference: “With a positive liquid biopsy, patients receive a standard adjuvant chemotherapy, the same used a oggi per il trattamento di tutti i tumori del colon di stadio II ad alto rischio e in stadio III (a base di capecitabina e oxaliplatino, un trattamento molto attivo contro il cancro del colon, ma anche con una certa tossicità neurologica, acuta e cronica , ed.)”. Se la biopsia liquida è negativa, invece, i pazienti ricevono una terapia più leggera, che prevede la somministrazione della sola capecitabina. La biopsia liquida viene effettuata più volte nel corso del trattamento durante il follow-up dei pazienti “per rilevare un’eventuale resistenza innata del tumore alla terapia e guidare la rimodulazione del regime chemioterapico”, aggiunge Lonardi.
A new paradigm: therapy is not the same for everyone
“The results we have obtained will now have to be confirmed by those of various ongoing international studies which also include a direct comparison with standard therapy. “If they are validated – concludes Marsoni – they will be able to contribute on the one hand to modifying the guidelines for the treatment of operable colon cancer, reducing or completely eliminating adjuvant therapy in patients with negative liquid biopsy. On the other hand, they will be able to help choose the therapy for the type of tumor and the individual patient in a more precise and targeted way, in the event of a lack of molecular response. Pegasus can not only make an important contribution to changing the current paradigm of a one-size-fits-all chemotherapy with respect to the new paradigm of a more targeted and precise therapy, but it could also allow us to explore the biology of micro-metastatic tumors, those for which we must find new and more effective therapies”.