Oncotype DX Identifies Stage II-III Colon Cancer with Higher Risk of Recurrence

Oncotype DX identifies colon cancers with high risk of recurrence and helps determine necessity of adjuvant chemotherapy

by Dr. C.H. Weaver M.D. updated 3/2019

Among patients with early stage II or III colon cancer, the OncotypeDX colon cancer test provides information about the risk of cancer recurrence and may help guide treatment decisions.

Gene expression profiling explores the patterns of genes that are active in tumor cells. Studies suggest that gene expression may provide important information about prognosis or likely response to treatment in several types of cancer. For example, among women with early-stage, estrogen receptor-positive breast cancer, the OncyotypeDX breast cancer test has been shown to predict the likelihood of cancer recurrence and the likelihood of benefit from chemotherapy. As a result, the test has been added to medical guidelines for early-stage breast cancer.

The Oncotype DX colon cancer test evaluates 12 genes in a sample of tumor tissue and generates a Recurrence Score. The Recurrence Score provides information about the likelihood of cancer recurrence—and as a result, can improve treatment decisions.

A similar test may provide important information for patients with stage II and III colon cancer. Stage II colon cancer refers to cancer that extends through the wall of the colon but has not invaded lymph nodes or spread to distant parts of the body. Many patients with stage II disease have good outcomes with surgery alone, and routine adjuvant (post-surgery) chemotherapy is not currently recommended for all individuals with stage II colon cancer. Chemotherapy may, however, be considered for stage II patients with a higher risk of cancer recurrence.

In a large clinical study, the OncotypeDX Recurrence Score and other factors were evaluated among patients with stage II colon cancer who participated in the CALGB 9581 study.

  • These results confirmed that the rs such as stage, grade, number of lymph nodes examined, and mismatch repair (MMR) protein status, the OncotypeDX eRecurrence Score was a significant predictor of recurrence risk.
  • The researchers also evaluated the Recurrence Score in a subset of patients for whom traditional factors such as grade do not provide prognostic information (patients with T3 stage II cancer and intact MMR protein function). Once again, the Recurrence Score was able to identify patients who had a high risk of cancer recurrence: five-year risk of recurrence was more than 20% among patients with the highest Recurrence Scores.

These results confirm that the OncotypeDX colon cancer test provides new information about recurrence risk in patients with stage II colon cancer and may help guide treatment decisions by identifying patients with more aggressive disease.

Oncotype DX Changes Treatment Recommendations in Stage II Colon Cancer

According to the results of a study published in Current Medical Research and Opinion use of the Oncotype DX® colon cancer test changed treatment recommendations in 29 percent of stage II colon cancer patients

The Partnership for Health Analytic Research (PHAR) performed a clinical utility analysis of the Oncotype DX colon cancer test and found that that use of the assay changes treatment recommendations in 29 percent of stage II colon cancer patients.

The PHAR clinical decision impact survey of physicians who ordered the Oncotype DX colon cancer test showed that knowledge of a patient’s Recurrence Score® is associated with changes in the medical oncologists’ treatment recommendations in 29 percent of cases. Two-thirds (67 percent) of changes in treatment recommendations were decreases in treatment intensity (changes from chemotherapy to observation or from oxaliplatin-containing chemotherapy to treatment with fluoropyrimidine monotherapy), while one-third (33 percent) of changes were increases in treatment intensity.

The researchers concluded that the Recurrence Score changed treatment recommendations in 29 percent of patients with stage II colon cancer. Use of the assay might lead to reductions in treatment intensity.

Oncotype DX Predicts Recurrence Risk in Stage II and Stage III Colon Cancer

The Oncotype DX colon cancer test became available for use in stage II colon cancer patients in 2010. Although the test was originally developed for use in patients with stage II disease it was ultimately also validated for use in patients with stage III colon cancer.

To assess the ability of the test to predict recurrence risk researchers evaluated 892 patients with stage II-III colon cancer. The patients were enrolled in a clinical trial that assessed two different approaches to adjuvant (post-surgery) chemotherapy: patients were treated with 5FU/LV alone or in combination with oxaliplatin. The addition of oxaliplatin increased effectiveness, but also increased side effects.

  • The Recurrence Score predicted recurrence risk in both Stage II and Stage III colon cancer.
    • Among 5FU-treated patients with Stage II cancer, the five-year risk of recurrence was 9% among those with a low Recurrence Score, 13% among those with an intermediate Recurrence Score, and 18% among those with a high Recurrence Score.
    • Among 5FU-treated patients with Stage IIIA/B cancer, the five-year risk of recurrence was 21% among those with a low Recurrence Score, 29% among those with an intermediate Recurrence Score, and 38% among those with a high Recurrence Score.
    • Among 5FU-treated patients with Stage IIIC cancer, the five-year risk of recurrence was 40% among those with a low Recurrence Score, 51% among those with an intermediate Recurrence Score, and 64% among those with a high Recurrence Score.
  • The Recurrence Score remained an important predictor of risk even after accounting for other characteristics of the cancer.
  • In addition to predicting the risk of recurrence, the Recurrence Score also provided information about overall survival.
  • When looking at the benefit of adding oxaliplatin, the absolute benefit (but not the relative benefit) was greater for patients with higher Recurrence Scores.

These results confirm that the Oncotype DX colon cancer test provides information about risk of recurrence among patients with Stage II and Stage III colon cancer, and the test is now available for patients with both stages of disease.

OncotypeDX Associated with Stage II Disease While Increasing Patient Well-being & Reducing Medical Costs

Genomic Health, Inc. announced that PharmacoEconomics published positive results from a health economic analysis suggesting that use of the Oncotype® DX colon cancer test may result in a significant reduction in direct medical costs and improve patient quality of life by helping them avoid side effects of unnecessary treatment.

“By providing quantitative information which has not been available with conventional measures, as demonstrated in this analysis, the Oncotype DX colon cancer test is likely to lead to both savings in direct medical costs and improved patient well-being,” said Steven Alberts, M.D., chair, division of Medical Oncology at the Mayo Clinic, Rochester, Minn.

The analysis of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium demonstrated the value of using the Oncotype DX test to identify stage II colon cancer patients with low risk of recurrence, who may consider forgoing a chemotherapy regimen. After physicians received the Recurrence Score results, their recommendations for adjuvant chemotherapy in patients with low risk of recurrence decreased by 22 percent, which resulted in direct medical care cost savings of approximately $1,000 per patient. This is the first health economic study of the Oncotype DX colon cancer test conducted in clinical practice. A previous, separate modeling study showing that the use of the Oncotype DX test in stage II colon cancer patients may lead to health care cost savings while improving clinical outcomes was published in 2012 by Value of Health.

“This publication highlights the important role of the Oncotype DX colon cancer test in delivering personalized medicine to the modern paradigm for cancer care,” said George Kim, M.D., gastrointestinal oncologist, 21st Century Oncology, Jacksonville, Fla. “By enabling a more individualized approach to my patients’ treatment, the test not only saves health care dollars but also improves their well-being and can prevent individual non-direct costs associated with potentially unnecessary treatment, related time away from work and increased household care needs. This trial is an important landmark highlighting the advantages of individualized care in terms of treatment benefit, toxicity and cost.” (4)

Oncotype DX Validated in Stage II and III Colon Cancer

The Oncotype DX® Recurrence Score® (RS) results predict recurrence risk in stage II and III colon cancer and may better inform adjuvant therapy decisions in this population, according to the results of a validation study published in the Journal of Clinical Oncology.

This is the first study to validate Oncotype DX in patients with stage III disease.In the large, independent validation study Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens and then analyzed by Cox regression, adjusting for stage and treatment. The results indicated that the Recurrence Score results predicted risk of recurrence, disease-free survival and overall survival in stage II and stage III colon cancer patients receiving adjuvant chemotherapy.

The results provide additional information beyond conventional risk factors, enabling better discrimination of absolute benefit of chemotherapy as a function of risk. Patients with a high Recurrence Score result can be expected to derive larger absolute chemotherapy treatment benefit than patients with a low Recurrence Score result in both stage II and stage III colon cancer.The researchers concluded that the Recurrence Score predicts recurrence risk in stage II and stage III colon cancer. The test provides quantitative and individualized risk assessment that helps guide chemotherapy treatment decisions. (5)

Oncotype DX Changes Treatment Recommendations in Stage II Colon Cancer

The PHAR clinical decision impact survey of physicians who ordered the Oncotype DX colon cancer test showed that knowledge of a patient’s Recurrence Score® is associated with changes in the medical oncologists’treatment recommendations in 29 percent of cases. Two-thirds (67 percent) of changes in treatment recommendations were decreases in treatment intensity (changes from chemotherapy to observation or from oxaliplatin-containing chemotherapy to treatment with fluoropyrimidine monotherapy), while one-third (33 percent) of changes were increases in treatment intensity.The researchers concluded that the Recurrence Score changed treatment recommendations in 29 percent of patients with stage II colon cancer. Use of the assay might lead to reductions in treatment intensity. (6)

References:

  1. Venook AP, Niedzwiecki D, Lopatin M et al. Validation of a 12-gene colon cancer recurrence score (RS) in patients (pts) with stage II colon cancer (CC) from CALGB 9581. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3518.
  2. Cartwright T, Chao C, Lee M, et al. Effect of the 12-Gene Colon Cancer Assay Results on Adjuvant Treatment Recommendations in Patients with Stage II Colon Cancer. Current Medical Research and Opinion. Published online November 7, 2013: doi:10.1185/03007995.2013.855183.
  3. O’Connell M, Lee M, Lopatin M et al. Validation of the 12-gene colon cancer recurrence score (RS) in NSABP C07 as a predictor of recurrence in stage II and III colon cancer patients treated with 5FU/LV (FU) and 5FU/LV+oxaliplatin (FU+Ox). Paper presented at: 2012 Annual Meeting of the American Society of Clinical Oncology; June 1-5, 2012;Chicago,IL. Abstract 3512.
  4. Yothers G, O’Connell MJ, Lee M, et al. Validation of the 12-Gene colon cancer Recurrence Score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. Journal of Clinical Oncology. 2013; 31(36): 4512-4519.
  5. Venook AP, Niedzwiecki D, Lopatin M, et al. Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581. Journal of Clinical Oncology. Published early online March 25, 2013. doi: 10.1200/JCO.2012.45.1096
  6. Cartwright T, Chao C, Lee M, et al. Effect of the 12-Gene Colon Cancer Assay Results on Adjuvant Treatment Recommendations in Patients with Stage II Colon Cancer. Current Medical Research and Opinion. Published online November 7, 2013: doi:10.1185/03007995.2013.855183

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