Circulating Tumor DNA as a Predictive Biomarker in Adjuvant Chemotherapy for Patients with Stage 2A Colon Cancer (COBRA)

Verbus, Emily; Rossi, Antonello; Luna, A.; Iqbal, Atif; Morris, Van K.; Hernandez, Jonathan M.

doi:10.1245/s10434-021-10112-z

Cited by 11 publications

(4 citation statements)

References 6 publications

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“…However, a longer follow-up would be needed to validate these findings and exclude a substantial benefit of ACT in these patients. Indeed, several prospective studies are investigating the omission of ACT for patients with ctDNA-negative status after surgery 19 , 20 . However, as the bias of patient characteristics is inevitable in observational studies, we are conducting a randomized, phase III VEGA trial to assess the noninferiority of observation alone compared with standard ACT in patients with high-risk stage II or low-risk pathological stage III CRC who are confirmed to be ctDNA negative 4 weeks after surgery.…”

Section: Discussionmentioning

confidence: 99%

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer

Kotani

Oki

Nakamura

et al. 2023

Nat Med

169

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Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II–IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49–24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.

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Section: Discussionmentioning

confidence: 99%

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer

Kotani

Oki

Nakamura

et al. 2023

Nat Med

169

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“…Second, decide which regimen will maximize efficacy and minimize adverse effects. For the first step, ctDNA biomarkers are promising in identifying patients whose cancer will likely recur to facilitate decision making, [19][20][21] and large-scale clinical trials studying the utilities of ctDNA are ongoing (ClinicalTrials.gov identifiers: NCT04068103 and NCT05174169). Our study addressed the need to facilitate decision making in the second step.…”

Section: Discussionmentioning

confidence: 99%

“…2 Multiple biomarkers have been developed for predicting the recurrence risk of adjuvant CC patients, aiming to save lowrisk patients from unnecessary treatment. [16][17][18] In particular, circulating tumor DNA (ctDNA) biomarkers [19][20][21] are promising in identifying patients whose cancer will likely recur. However, such risk-oriented biomarkers/models may not predict whether a patient will benefit from oxaliplatin if treatment is warranted.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer

Chen,

Wang,

Cai

et al. 2024

JCO

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PURPOSE A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects. METHODS We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS– (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect. RESULTS Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS–. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS– patients did not (COLOXIS– HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65). CONCLUSION The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.

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“…Finally, active enrollment in ongoing clinical trials that are incorporating the plasma-only or the tumor-informed assays is going to be key in understanding the implications of a positive test result and the role of ctDNA as a predictive marker. 13 …”

Section: Discussionmentioning

confidence: 99%

Tumor-Informed Versus Plasma-Only Liquid Biopsy Assay in a Patient With Multiple Primary Malignancies

Kasi

2022

JCO Precision Oncology

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Circulating Tumor DNA as a Predictive Biomarker in Adjuvant Chemotherapy for Patients with Stage 2A Colon Cancer (COBRA)

Cited by 11 publications

References 6 publications

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer

Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer

Tumor-Informed Versus Plasma-Only Liquid Biopsy Assay in a Patient With Multiple Primary Malignancies

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