ctDNA effectively detects cases of stage II colon cancer where adjuvant chemotherapy can be avoided

Postoperative circulating tumor DNA (ctDNA) status can be effectively used to avoid adjuvant chemotherapy, according to the results of a Phase 2 DYNAMIC study presented at the 2022 ASCO Annual Meeting, Stage II. Maintains a recurrence-free survival rate for patients with colorectal cancer.Published at the same time New England Journal of Medicine..^1,2

In this study, patients were randomized to a ctDNA-guided treatment cohort (n = 294) or standard of care group (n = 147). Patients who were negative for ctDNA in the guided cohort were given the opportunity to discontinue chemotherapy, and those who were positive for ctDNA were given adjuvant chemotherapy. Overall, 15% of patients received chemotherapy in this group, compared with 28% in the standard-of-care group, and the decision was based on standard clinical factors (relative risk). [RR]1.82; 95% CI, 1.25-2.65).

Despite less treatment in the ctDNA group, recurrence-free survival (RFS) rates were similar between the two groups. The 2-year RFS rate for the ctDNA guided cohort was 93.5%, compared with 92.4% in the standard of care group (1.1 percentage point difference; 95% CI, –4.1 to 6.2). The three-year RFS rates were 91.7% and 92.4%, respectively (HR, 0.96; 95% CI, 0.51-1.82). In addition, the study found that patients with ctDNA-positive tumors had better results when treated with oxaliplatin-based doublets compared to single-agent fluoropyrimidine therapy.

“The strategy of using ctDNA results to inform treatment has almost halved the number of patients receiving postoperative chemotherapy from 28% to 15%. In stage II colon cancer patients, surgery Later ctDNA evaluation will enable more accurate prediction of recurrence and patient selection for postoperative treatment, “said Dr. Genetai, lead author and associate professor at the Walter and Elizahall Institute of Medicine. increase. Peter McCallum Cancer Center, Victoria, Australia. “Although the proportion of patients receiving chemotherapy with ctDNA guidance is low, the chances of survival and cancer elimination after 3 years are the same as standard management.”

The study, conducted in Australia and New Zealand between 2015 and 2019, completed ctDNA analysis of 99% of guidearms (291 of 294). Two patients had not received ctDNA-guided treatment. In this group, 45 patients were ctDNA positive and all but one received chemotherapy. Chemotherapy was not given to postoperative ctDNA-negative patients (n = 249) except for one patient.

The characteristics matched evenly among the groups. The median age of patients in this study was 64 years, with 27% over 70 years. The most common ECOG performance status was 0 (80%), with tumors evenly distributed on the left (46%) and right (54). %) The side of the colon. The stage of the tumor was mainly T3 (85%) and the rest was T4. Other features include poor tumor differentiation (14%), lymph node yield <12 (5%), tumor perforation (3%), intestinal obstruction (10%), and vascular invasion (27%). 40% of patients were considered high risk at baseline.

In addition to avoiding chemotherapy in some patients, knowing that patients were ctDNA positive increased the use of oxaliplatin-based doublet chemotherapy. In the ctDNA-induced group, 62% of patients received the oxaliplatin-based doublet, compared to only 10% in the standard group. Single-agent fluoropyrimidine therapy was used in 90% of patients in the standard group and 38% of patients in the ctDNA-guided group.

The median time from surgery to the start of chemotherapy was 83 days in the ctDNA group compared to 53 days in the standard group. The median duration of treatment was 24 weeks in both groups, and the main cause of discontinuation was the completion of planned treatment. A median of 84% of patients in the standard group received the full dose compared to 78% in the ctDNA group.

Fewer chemotherapy was used with the ctDNA-guided approach in all patient subgroups, except for patients with lymph node yields <12 and those over 70 years who were less likely to receive chemotherapy in the standard treatment group. The biggest difference in the use of chemotherapy is less preferred in the ctDNA-induced group, with T4 tumors (RR, 2.57; 95% CI, 1.46-4.50) and high-risk characteristics (RR, 2.14; 95% CI, 1.43). It was a patient. -3.21), and poorly differentiated tumors (RR, 5.06; 95 CI, 1.02-25.10).

In the guided cohort, relapse or death occurred in 6% of patients with ctDNA-negative status compared to 18% in the ctDNA-positive group. The estimated 3-year RFS rate was 92.5% in patients in the ctDNA-negative group who did not receive chemotherapy, compared with 86.4% in patients who were ctDNA-positive treated with chemotherapy (HR, 1.83; 95%). CI, 0.79-4.27). In addition, there were differences in RFS depending on the type of chemotherapy used within the ctDNA-positive group, with a 3-year RFS rate of 92.6% for patients receiving oxaliplatin-based doublets, compared with 76.0% for single-agent fluoropyrimidine therapy. was.

“Patients with negative ctDNA results have a very low risk of recurrence despite not receiving chemotherapy, suggesting that postoperative therapy is unlikely to benefit patients in this group. “Tie said. “The ctDNA-based approach can reduce the number of patients treated with chemotherapy without compromising the risk of recurrence. Given the good results of chemotherapy-treated ctDNA-positive patients, this clearly A defined high-risk patient subgroup may benefit substantially from treatment. “

Post-hoc analysis of the data sought to further improve treatment choices by combining clinical features with ctDNA status. In ctDNA-negative patients who did not receive chemotherapy, the 3-year RFS rate was 96.7% in patients with clinically low-risk features, compared with 85.1% in patients with high-risk features (HR, 3.04). 95% CI, 1.26-). 7.34). Patients with T3 tumors with ctDNA negative status showed a 3-year RFS rate of 94.2% compared to 81.3% of patients with T4 tumors (HR, 2.60l 95% CI, 1.01-6.71).

“Liquid biopsy can be a useful tool for guiding treatment decisions,” said ASCO Expert Cathy Eng, MD, FACP and FASCO of Vanderbilt-Ingram Cancer Center in a statement. “Thanks to the results of this study, we better identify which patients with stage II colorectal cancer benefit from postoperative treatment with chemotherapy and which patients can avoid additional treatment without compromising recurrence. May be able to use it for-free survival. “

References

1. Tie J, Cohen JD, Lahouel K, et al. Adjuvant chemotherapy guided by circulating tumor DNA analysis in stage II colon cancer: Randomized dynamic trial. J Clin Oncol.. 2022; 40 (suppl 17; abstr LBA100). Doi: 10.1200 / JCO.2022.40.17_suppl.LBA100
2. Circulating tumor DNA analysis leading to adjuvant therapy in Tie J, Cohen JD, Lahouel K, and other stage II colon cancers. N Engl J Med.. Published online June 4, 2022. doi: 10.1056 / NEJMoa2200075