The adjuvant oxaliplatin-irinotecan paradox.

Abstract

e15655 Background: A pervasive pattern in oncology is that chemotherapeutic agents which achieve acceptance for adjuvant use are the ones that have shown superior efficacy in the treatment of metastatic disease. The greater the efficacy in metastatic disease, the greater the likelihood that adjuvant use will be statistically viable. Oxaliplatin is the exception to this, having paradoxically shown similar outcomes to irinotecan in metastatic colorectal cancer (CRC) but superiority in the adjuvant setting. In this study, the TriNetX research database was used to better evaluate the adjuvant efficacy of oxaliplatin use in real-world patients. Methods: The TriNetX research database was used for this study. The TriNetX platform provides access to anonymized medical record information on more than 91 million patients in 75 large healthcare organizations. Three cohorts of stage III colorectal patients were created for comparison, utilizing International Classification of Disease-10 (ICD-10) codes and medication codes provided in the TriNetX platform. All patients were required to have a diagnosis of colon cancer (C18) and lymph node involvement (C77), with the absence of any liver or lung metastases (C78.7 and C78.0, respectively). Adjuvant oxaliplatin use was identified by the presence of the oxaliplatin medication code within 9 months of CRC diagnosis. The adjuvant oxaliplatin cohort was compared to a cohort with no oxaliplatin exposure, identified by the exclusion of the oxaliplatin medication code for 12 months following CRC diagnosis. The cohorts were balanced for age, race, gender, and ethnicity. The endpoint of the comparisons was all-cause mortality at 5 years. Results: Adjuvant use of oxaliplatin was associated with a 2.3% absolute decrease in the risk of death at 5 years (risk ratio 0.88, 95% CI (0.79,0.97), p-value 0.01). See figure 1. Conclusions: This study shows that adjuvant use of oxaliplatin is associated with a 2.3% absolute survival advantage in stage III colorectal cancer patients. This small absolute benefit is likely why occasional retrospective analyses have been unable to replicate it. A controlled interrupted time series analysis from Huang, et. al. showed no benefit to adjuvant oxaliplatin in the stage III setting for Taiwanese patients. Such a small benefit may also explain why the ACHIEVE trial found three months of adjuvant oxaliplatin to be equivalent to six. When a benefit is very small, a shorter duration of treatment would be more likely to result in statistical equivalency than if the benefit was more substantial. [Table: see text]