Effectiveness of adjuvant FOLFOX vs 5FU/LV in adults over age 65 with stage II and III colon cancer using a novel hybrid approach

• Published in: Pharmacoepidemiology and drug safety 2020-12, Vol.29 (12), p.1579-1587
• Main Authors: Lund, Jennifer L., Webster‐Clark, Michael A., Hinton, Sharon Peacock, Shmuel, Shahar, Stürmer, Til, Sanoff, Hanna K.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; aging; cancer; Cancer therapies; Chemotherapy; Clinical trials; Colon cancer; Colorectal cancer; comparative effectiveness research; Epidemiology; Medicare; Mortality; Oxaliplatin; Patients; pharmacoepidemiology
• ISSN: 1053-8569; 1099-1557
• DOI: 10.1002/pds.5148

Purpose Estimates of cancer therapy effects can differ in clinical trials and clinical practice, partly due to underrepresentation of certain patient subgroups in trials. We utilize a hybrid approach, combining clinical trial and real‐world data, to estimate the comparative effectiveness of two adjuvant chemotherapy regimens for colon cancer. Methods We identified patients aged 66 and older enrolled in the Multicenter International Study of Oxaliplatin/5FU‐LV in the Adjuvant Treatment of Colon Cancer. Similar patients were identified in the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database, initiating adjuvant chemotherapy with either 5‐fluorouracil (5FU) alone or in combination with oxaliplatin (FOLFOX). We used logistic regression to estimate the likelihood of trial enrollment as a function of age, sex, and substage. Using inverse odds of sampling weights (IOSW), we compared 5‐year mortality in patients randomized to FOLFOX vs 5FU using weighted Cox proportional hazards regression, the Nelson‐Aalen estimator for cumulative hazards, and bootstrapping for 95% confidence intervals (CIs). Results There were 690 trial participants and 3834 SEER‐Medicare patients. The SEER‐Medicare population was older and had a higher proportion of stage IIIB and IIIC patients than the trial. After controlling for differences between populations, the IOSW 5‐year HR was 1.21 (0.89, 1.65), slightly farther from the null than the trial estimate (HR = 1.14, 95%CI: 0.87, 1.49). Conclusions This study supports mounting evidence of little to no incremental reduction in 5‐year mortality for FOLFOX vs 5FU in older adults with stage II‐III colon cancer, emphasizing the importance of combining clinical trial and real‐world data to support such conclusions.