LB802 - Results Of ctDNA As A Predictive Biomarker In Adjuvant Chemotherapy In Stage II Colon Cancer: NRG-GI005 (COBRA) Phase II/III study

Monday, June 3, 2024

3:55 PM – 4:01 PM ET, USA

Location: Room 314-317

Author(s)

Atif iqbal, MD, F.A.C.S., F.A.C.R.S (he/him/his)

Associate Professor & Chief, Colorectal Surgery; Assist. Vice Chair Quality
Baylor College of Medicine, Houston TX
Baylor College of Medicine, Houston TX
HOUSTON, TX, United States

All relevant financial disclosures have been managed and will be listed below.
This individual has no financial relationships with ineligible companies.

Author(s)

VM

Van Morris, MD

Associate Professor
MD Anderson Cancer Center
Houston, Texas, United States

Disclosure information not submitted.

Senior Author(s)

TG

Thomas J. George, MD

Deputy Director
University of Florida Health Cancer Center
Gainesville, Florida, United States

Disclosure information not submitted.

Author(s)

GY

Greg Yothers, PhD

Research Professor of Biostatistics
Department of Biostatistics, University of Pittsburgh School of Public Health; NRG Oncology Statistical and Data Management Center
Pittsburgh, Pennsylvania, United States

Disclosure information not submitted.
SK

Scott Kopetz, MD, PhD

Associate Vice President, Translational Integration
University of Texas MD Anderson Cancer Center
Houston, Texas, United States

Disclosure information not submitted.
SP

Shannon L. Puhalla, MD

Medical Oncologist
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States

Disclosure information not submitted.
PL

Peter C. Lucas, MD, PhD

Vice Chair of Research for Laboratory Medicine and Pathology
Mayo Clinic
Rochester, Minnesota, United States

Disclosure information not submitted.
PB

Patrick Boland, MD

MD
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States

Disclosure information not submitted.
DD

Dustin A. Deming, MD

Associate Professor
Univesity of Wisconsin
Madison, Wisconsin, United States

Disclosure information not submitted.
AS

Aaron Scott, MD

MD
University of Arizona Cancer Center
Tucson, Arizona, United States

Disclosure information not submitted.
HL

Howard Lim, MD

MD
BC Cancer - Vancouver
Vancouver, British Columbia, Canada

Disclosure information not submitted.
TH

Theodore S. Hong, MD

Radiation Oncologist
Massachusetts General Hospital Cancer Center; and Harvard Medical School
Boston, Massachusetts, United States

Disclosure information not submitted.
NW

Norman Wolmark, MD

Chair
NSABP Foundation, Inc.; UPMC HIllman Cancer Center; and University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States

Disclosure information not submitted.

Abstract Podium Presenter(s)

Yesenia Rojas-Khalil, MD (she/her/hers)

Assistant Professor
Baylor College of Medicine
Houston, TX, United States

All relevant financial disclosures have been managed and will be listed below.
This individual has no financial relationships with ineligible companies.

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Purpose/Background: For patients (pts) with colon cancer (CC), the detection of circulating tumor DNA (ctDNA) is associated with persistent disease after resection and outperforms traditional clinical and pathological features in prognosticating recurrence risk. We hypothesized that for pts with low-risk stage II CC, a positive ctDNA status after resection may identify those who benefit from adjuvant chemotherapy.

Methods/Interventions: In this prospective phase II/III clinical trial, pts with resected stage II CC without traditional high risk features and whom the evaluating oncologist deems suitable for active surveillance (i.e., not needing adjuvant chemotherapy) were randomized 1:1 to two arms: standard-of-care/observation (Arm A), or ctDNA assay directed therapy (Arm B). Postoperative blood was analyzed for ctDNA with the Guardant LUNAR assay, covering CC-relevant mutations and CC-specific methylation profiling. Arm B pts with ctDNA detected were treated with 6 mos of adjuvant (CAPOX or FOLFOX) chemotherapy. Primary endpoint for the phase II study was clearance of ctDNA at the 6-mo timepoint. A 1- sided Fisher exact test was used to compare ctDNA clearance between Arm A and Arm B among the first 16 pts with ctDNA detected at baseline. If p..35, the study would be stopped for futility of ctDNA clearance but would otherwise continue to phase III if p#.35. We present the results of the pre-planned phase II analysis.

Results/Outcomes: 635 pts were randomized (Arm A: 318; Arm B: 317).One pt with ctDNA detected in Arm B declined protocol-directed chemotherapy but was included in the intention to treat analysis. Among the first 16 pts with ctDNA detected at baseline for the primary endpoint analysis, clearance of ctDNA after 6 mos was observed in 3/7 pts (43%, 95% CI 10-82%) in the control arm and in 1/9 pts (11%, 95% CI 0.3-48%) in the experimental arm after chemotherapy (p=.98). There were no unanticipated toxicities in those treated with chemotherapy.

Conclusion/Discussion: The phase II endpoint was not met and further enrollment has been halted based upon pre-specified study stopping rules utilizing the original assay. No improvement in ctDNA clearance was observed after 6 mos of chemotherapy for pts with ctDNA detected following resection of stage IIA CC. Future trials evaluating ctDNA as an integral biomarker for minimal residual disease determination must account for assay specificity in this pt population.

Support: U10CA180868, -180822; UG1CA189867; GuardantHealth.Clinical trial information: NCT04068103. Research Sponsor: NIH; GuardantHealth.