‘Disappointing’ results question the utility of liquid biopsy-guided cancer treatment
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Key takeaways:
- Patients who had detectable ctDNA after resection of stage II colon cancer did not benefit from adjuvant chemotherapy.
- Unsuccessful results lead to termination of the phase 2/phase 3 trial.
Circulating tumor DNA did not successfully predict whether patients with resected stage II colon cancer would benefit from adjuvant chemotherapy, according to findings presented at ASCO Gastrointestinal Cancers Symposium.
Results prompted researchers to stop the prospective phase 2/phase 3 clinical trial looking at the efficacy of using circulating tumor DNA (ctDNA) to determine if this patient population should get secondary treatment.
“The real-world applications of liquid biopsy for patients with gastrointestinal cancers continue to evolve rapidly,” Van K. Morris, MD, associate professor at The University of Texas MD Anderson Cancer Center, said in an ASCO press release. “While the results of this specific trial are disappointing, continued enhancements to ctDNA assay characteristics and performance coupled with the unmet clinical needs of patients keep future ctDNA trials highly relevant for the foreseeable future.”
Background and methodology
The presence of ctDNA has been a predictor of recurrence for patients with colon cancer, according to background information provided by the study’s investigators.
Additionally, patients who experienced ctDNA clearance through adjuvant chemotherapy have improved survival outcomes based on other observational studies, Morris said during his ASCO GI presentation.
“We hypothesized that for patients with low-risk, stage II colon cancer, a positive ctDNA status after resection may identify those who benefit from adjuvant chemotherapy,” researchers wrote.
Morris and colleagues built a study cohort of 635 patients with resected stage II colon cancer. Patients did not have high-risk features and oncologists recommended they receive active surveillance.
Researchers randomly assigned patients in a 1:1 ratio to receive either standard care or ctDNA assay-directed therapy. Patients in the experimental arm who had evidence of ctDNA received 6 months of adjuvant chemotherapy.
Results and clinical implications
Of the first 16 patients with ctDNA, seven received standard care as part of the control arm and nine had adjuvant chemotherapy.
For the control group, 43% of those patients did not have ctDNA detected after 6 months (95% CI; 10-82), whereas only 11% of the cohort that received chemotherapy had evidence of ctDNA clearance (95% CI; 0.3-48; P = 0.98).
Trial parameters dictated it would stop if a probability value of greater than 0.35 occurred among the first 16 patients.
“The consideration of adjuvant chemotherapy in the stage II setting has always remained a shared decision-making process,” Cathy Eng, MD, FACP, FASCO, professor of medicine in the department of hematology and oncology at Vanderbilt-Ingram Cancer Center, said the ASCO release.
“The consideration of ctDNA positivity was in the hopes as a surrogate marker to guide the use of adjuvant chemotherapy by attaining ctDNA clearance at 6 months,” she added. “While the investigators’ pre-planned interim analysis was unable to determine any improvement in ctDNA clearance, the role of ctDNA must continue to be explored.”
References:
- ASCO GI 2024: New study adds to ambiguity of role of post-operative ctDNA to guide treatment in patients with low-risk, stage IIA colon cancer (press release). Available at: https://old-prod.asco.org/about-asco/press-center/news-releases/new-study-adds-ambiguity-role-post-operative-ctdna-guide. Posted Jan. 22, 2024. Accessed: Jan. 25, 2024.
- Morris VK, et al. Abstract 5. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 18-20, 2024; San Francisco.
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Morris VK, et al. Abstract 5. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 18-20, 2024; San Francisco.
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