Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis

Author(s): Benoist Chibaudel, MD¹; Morteza Raeisi, PhD²; Romain Cohen, MD, PhD³; Greg Yothers, PhD⁴; Richard M. Goldberg, MD⁵; Jean-Baptiste Bachet, MD⁶; Norman Wolmark, MD⁷; Takayuki Yoshino, MD, PhD⁸; Hans-Joachim Schmoll, MD⁹; Rachel Kerr, MD¹⁰; Sara Lonardi, MD¹¹; Thomas J. George, MD¹²; Einat Shacham-Shmueli, MD¹³; Qian Shi, PhD¹⁴; Thierry André, MD^3,2; Aimery de Gramont, MD^2,1

Source: https://doi.org/10.1200/JCO.24.00394

Dr. Maen Hussein's Thoughts

No oxaliplatinum in stage 2 colon cancer, even high-risk patients, by the way, De Gramont is one of the authors (father of FOLOFX reigmens).

PURPOSE

The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined.

PATIENTS AND METHODS

One thousand five hundred and ninety-five patients with stage II CC receiving FP or FPOX were pooled. The overall survival (OS) benefit of OX was analyzed using Kaplan-Meier curves and unadjusted Cox models stratified by study. Three thousand and fifty-nine patients with stage III CC were used only for interaction tests between the allocated chemotherapy and stage.

RESULTS

In the pooled analysis of stage II patients, independent prognostic factors in multivariable analysis were sex, age, perforation/obstruction, and tumor sidedness. There was a significant interaction in OS between stage and allocated chemotherapy with hazard ratios (HRs) of 1.03 for stage II (95% CI, 0.82 to 1.29; P = .813) and 0.82 for stage III (95% CI, 0.73 to 0.92; P = .001; Pint = .073). There was no benefit from the addition of OX to FP for any of the prognostic factors. The number of high-risk factors tested was not predictive of OX benefit. According to the currently agreed clinicopathologic risk classification, no OS benefit of OX was observed, as HR was 0.86 (95% CI, 0.63 to 1.18; P = .349).

CONCLUSION

No OS benefit of adjuvant OX was found in high-risk stage II CC, regardless of the definition used to characterize tumors as having a high risk for recurrence. Hence, our analysis suggests that OX should not be the standard of care for adjuvant chemotherapy for stage II CC, even in high-risk patients.

Author Affiliations

¹Department of Medical Oncology, Franco-British Hospital, Fondation Cognacq-Jay, Cancérologie Paris Ouest, Levallois-Perret, France; ²Statistical Unit, ARCAD Foundation, Paris, France; ³Sorbonne Université and Department of Medical Oncology, Saint-Antoine Hospital, Paris, France; ⁴Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA; ⁵Department of Medicine, West Virginia University Cancer Institute, Morgantown, WV; ⁶Hepato-Gastroenterology and Digestive Oncology Department, Sorbonne University, Pitié Salpêtrière Hospital, APHP, Paris, France; ⁷NSABP Foundation, Pittsburgh, PA; ⁸Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; ⁹Division of Clinical Research in Oncology, Martin-Luther University Halle-Wittenberg, Halle/Saale, Germany; ¹⁰Department of Oncology, University of Oxford, Oxford, United Kingdom; ¹¹Medical Oncology, Veneto Institute of Oncology IOV—IRCCS, Padua, Italy; ¹²Division of Hematology and Oncology, University of Florida, Gainesville, FL; ¹³Sheba Medical Center at Tel-Hashomer, Tel Aviv University, Tel Aviv, Israel; ¹⁴Department of Quantitative Health Science, Mayo Clinic, Rochester, MN

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