DNA-guided approach to circulating tumor safely reduces the use of chemotherapy in colon cancer


Source/Disclosures

Source:

TieJ, et al. Abstract LBA100. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.


Disclosures: Conrad R Hilton Foundation, Eastern Health Research Foundation, John Templeton Foundation, Lustgarten Foundation, The Marcus Foundation, NIH, Sol Goldman Charitable Trust, and The Virginia and DK Ludwig Fund for Cancer Research supported the study. Tie does not report any relevant financial information. Please see the summary for all relevant financial disclosures from the researchers. Montagut does not report any relevant financial information. Vidal does not report any relevant financial information.


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CHICAGO — DNA analysis of circulating tumors has safely reduced the use of adjuvant chemotherapy without compromising recurrence-free survival in patients with stage II colon cancer, according to results from the phase 2 randomized trial DYNAMIC.

The results, presented at the ASCO annual meeting and published simultaneously in The New England Journal of Medicineshowed that patients with circulating tumor DNA (ctDNA) negative disease had a lower likelihood of benefiting from chemotherapy, while ctDNA-positive patients experienced a survival benefit from adjuvant chemotherapy .


DNA 1

Source: Adobe Stock.

Rationale and methods

“Most patients with stage II colon cancer are cured by their surgery to remove the bowel cancer, but about 20% will develop a recurrence in subsequent years,” Jeanne Tie, MD, MBChB, FRACP, lower gastrointestinal medical oncology and trial management at the Peter MacCallum Cancer Center in Australia, Healio told. “Treating all Stage II patients with chemotherapy will reduce the risk of recurrence by around 15%, but that means 20 patients need to be treated to benefit one patient.”

The goal of adjuvant chemotherapy is to eradicate micrometastases, she added.

Jeanne Tie, MD, MBChB, FRACP

Jeanne tie

“The challenge has been that these microscopic deposits of cancer cells are tiny and not visible during surgery or visible on X-ray images,” Tie said. “A ctDNA analysis can detect tiny amounts of DNA released by these invisible cells into the bloodstream, allowing us to identify patients who have micrometastases and who, therefore, should be offered chemotherapy. Conversely, when the blood test does not reveal ctDNA, the likelihood of micrometastases is very low and chemotherapy can be avoided without compromising the risk of recurrence.

The researchers sought to assess whether ctDNA-guided treatment could reduce the use of adjuvant chemotherapy without compromising the risk of recurrence in 455 patients with resected stage II colon cancer. They randomly assigned patients to either ctDNA-guided treatment (n=302) or physician-guided treatment (n=153).

The non-inferiority of the RFS rate at 2 years served as the primary endpoint, with the use of adjuvant chemotherapy as a secondary endpoint.

The median follow-up was 37 months.

Main findings

Overall, 15.3% of patients assigned to ctDNA-guided therapy received adjuvant chemotherapy compared to 27.9% of those assigned to physician-guided therapy (OR = 2.14; P = .002). The researchers noted the greatest difference in patients with T4 (OR = 6.22) or poorly differentiated tumors (OR = 6.31).

Among those who received adjuvant chemotherapy, oxaliplatin-based doublet was used more frequently than fluoropyrimidine alone among those in the ctDNA-guided treatment group compared to those who received physician-guided treatment (62 .2% versus 9.8%; P

The researchers also found that ctDNA-guided treatment was not inferior to standard management for RFS at 2 years (93.5% vs. 92.4%), an absolute difference of 1.1 points percentage (95% CI, -4.1 to 6.2). They reported 3-year RFS rates of 86.4% after using adjuvant chemotherapy in ctDNA-positive patients and, among ctDNA-negative patients, 92.5% without chemotherapy. adjuvant and 96.7% in a subgroup of patients at low clinical risk.

“We have shown that cDNA testing can differentiate patients with stage II colon cancer who need chemotherapy after surgery from those who have a very low risk of recurrence and can avoid treatment by safely,” Tie said. “Importantly, the use of chemotherapy is significantly reduced with the use of this ctDNA-based approach with no impact on the risk of recurrence.”

Look forward

“The ctDNA test has the potential to revolutionize the approach to chemotherapy in colon cancer patients – avoiding unnecessary chemotherapy treatments in the majority – and will accelerate the development of promising new treatment options,” said declared Tie. “We are currently conducting trials in stage III colon cancer and other types of cancer, such as pancreatic cancer and ovarian cancer.”

Several recommendations arise from this trial that may be useful when considering possible clinical implementation, Clara Montagut, MD, PhD, head of the gastrointestinal cancer unit and medical oncologist Joana Vidal, MD, both at Hospital del Mar in Barcelona, ​​Spain, wrote in an editorial accompanying the study published in The New England Journal of Medicine.

“The trial used a ctDNA test specifically designed for minimal residual disease applications with very high sensitivity, as well as serial blood samples for ctDNA analysis to reduce the risk of a false negative result. “, they wrote. “Logistically, prompt processing and short turnaround time for ctDNA results are essential to avoid delays in initiation of adjuvant chemotherapy. The present assay employed a tissue-based strategy in which ctDNA probes were customized based on specific mutations identified in tumor tissue. Although this strategy confers high sensitivity, tissue-independent strategies could also be valid while reducing the time to results.

New advances in technology will undoubtedly improve the performance of cDNA testing for minimal residual disease, including the incorporation of tumor-specific methylation profiles, they added.

References:

Montagut C and Vidal J. N Eng J Med. 2022;doi:10.1056/NEJMe2204625.
TieJ, et al. Abstract LBA100. Presented at: ASCO Annual Meeting; June 3-7, 2022;
Chicago.Tie J, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2200075.

For more information:

Jeanne tie, MD, MBChB, FRACP, can be contacted at [email protected]

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