NRG Oncology and the University of Pittsburgh demonstrate that a Machine Learning Model Predicts Oxaliplatin Benefit Using Data from Two NSABP Clinical Trials

February 06 2024

PITTSBURGH, PA— The current standard of care for treating patients with stage 3 colon cancer is to use adjuvant therapy with FOLFOX, a combination of the drugs fluorouracil, leucovorin, and oxaliplatin. Although effective, the use of oxaliplatin can lead to known adverse events, mainly neurotoxicity that may be chronic. NRG Oncology tested a new machine learning model that can predict which colon cancer patients could derive benefit from the addition of oxaliplatin and could ultimately allow physicians to tailor treatment regimens better for their patients. The model used data from the NSABP C-07 and C-08 trials, both studies that utilized oxaliplatin in the treatment of colon cancer. These trials were sponsored by the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis and conducted by the National Cancer Institute clinical trials Network Groups. Oxaliplatin was provided by Sanofi under a Cooperative Research and Development Agreement (CRADA) with NCI for both trials; and bevacizumab was provided by Genentech under a CRADA with NCI. The results were recently published in the Journal of Clinical Oncology.

The model, named “COLOXIS” (colon oxaliplatin signature), was tested in 1,065 patients from the NSABP C-07 and C-08 studies. Of 1,065 patients, 421 were treated with 5-fluorouracil and leucovorin (FULV) and 644 were treated with FOLFOX. The model dichotomized patients into signature-positive and signature-negative. The signature-positive patients received benefit from oxaliplatin whereas the signature-negative patients did not.

“The goal of COLOXIS was to determine if we could isolate which patients benefit from the addition of oxaliplatin and which did not derive benefit. Understanding this could help minimize unnecessary adverse events for those who do not benefit,” stated Katherine L. Pogue-Geile, PhD, one of the corresponding authors of the research.

Among the 1,065 patients included, 526 were predicted as COLOXIS-positive (signature-positive) and 539 were predicted as COLOXIS-negative (signature-negative). The COLOXIS-positive prediction was associated with prognosis for FULV-treated patients (HR=1.52, 95%CI=1.07-2.15, P=0.017). The model was predictive of oxaliplatin benefit: COLOXIS-positive patients benefited from oxaliplatin (HR=0.65, 95%CI=0.48-0.89, P=0.0065, int P=0.03), but COLOXIS-negative patients did not (COLOXIS-negative HR=1.08, 95% CI=0.77-1.52, P=0.65).

These findings are a step to understanding the benefit of reserving the use of oxaliplatin containing regimens for specific patients. Further investigations are warranted to further validate this model with the goal of its application in clinical practice.

The PA Department of Health disclaims responsibility for any claims made in this report. This analysis was funded by the National Library of Medicine, National Cancer Institute at the National Institutes of Health, US Department of Health and Human Services, Public Health Service grants R01LM012011, LM013089, U10-CA180868, U10-CA180822, UG1-CA189867, and U24-CA196067, the Korea Health Technology R&D Project through the Korean Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant number HI13C2162; SP); Sanofi-Synthelabo; and Genentech.


Chen L, Wang Y, Cai C, Ding Y, Kim RS, Lipchik C, Gavin PG, Yothers G, Allegra CJ, Petrelli NJ, Suga JM, Hopkins JO, Saito NG, Evans T, Jujjavarapu S, Wolmark N, Lucas PC, Paik S, Sun M, Pogue-Geile KL, Lu X. Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer. J Clin Oncol. 2024 Feb 5:JCO2301080. doi: 10.1200/JCO.23.01080. Epub ahead of print. PMID: 38315963.

About NRG Oncology

NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.

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