Dr Kasi on the Rationale for Analyzing ctDNA to Inform Chemotherapy Decisions in CRC

Pashtoon Murtaza Kasi, MD, MS, oncologist, researcher, director, Colorectal Cancer Research, Weill Cornell Medicine, NewYork-Presbyterian Hospital, precision medicine director, Liquid Biopsy Research, the Englander Institute of Precision Medicine, discusses outcomes from an interim analysis of the BESPOKE CRC study (NCT04264702) and highlights the use of circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy treatment decisions for patients with stage II/III colorectal cancer (CRC).

In this study, the focus was on combining patients with stage II and III disease, a population that is different from what has previously been observed in existing studies, Kasi begins. Unlike other ongoing studies, the decision-making authority here was with the physician, rather than with the protocol, he says. Therefore, real-time results were provided, and the aspect of whether care should be escalated or de-escalated was investigated, Kasi explains. Notably, an innovative aspect of this investigation–possibly the first of its kind–was the inclusion of patient-reported outcomes (PROs), Kasi emphasizes.

Oncologists aimed to understand the impact of the ctDNA tests on patients and their sentiments regarding the results, such as questions about continued test usage, as well as anxiety, depression, or fear associated with the testing, Kasi elucidates. The ongoing debate about the psychological impact of such tests was formally addressed in this unique ctDNA study, a first-of-its-kind prospective study involving patients with CRC, he explains.

This study, aside from focusing on cancer outcomes, sought to capture PROs and long-term follow-up data, Kasi continues. Exploring the question of whether ctDNA is a predictive marker as well as a prognostic marker, the findings presented thought-provoking insights, he says. Overall, the benefits of adjuvant chemotherapy vs observation were evident in ctDNA-positive patients, showcasing a difference in disease-free survival (DFS) between the 2 cohorts. Importantly, chemotherapy wasn't a static variable, and converting ctDNA-positive patients to ctDNA-negative status demonstrated significant benefits, Kasi explains. Conversely, in ctDNA-negative patients, there was no difference in DFS between the adjuvant chemotherapy and observation cohorts, supporting ongoing studies investigating sparing ctDNA-negative patients from chemotherapy toxicity.

This study indicates that randomly assigning patients to a control arm without therapy might be a viable investigational option in future clinical trials, he expands. The question of avoiding chemotherapy in patients with stage III disease or those initially planned for chemotherapy is still under discussion, but these results bring a provocative perspective to the conversation, Kasi concludes.