A new publication by Jongeneel et al. from the DMC entitled “Estimating adjuvant treatment effects in stage II colon cancer: comparing the synthesis of randomized clinical trial data to real world data” has recently been published in the International Journal of Cancer.
Background of our study
There is an ongoing discussion regarding the impact of adjuvant chemotherapy in stage II colon cancer patients. Results from RCTs were not supportive of prescribing adjuvant chemotherapy to all stage II patients, although the conducted trials were not optimally designed to determine treatment effect in stage II colon cancer as patients with rectal cancer or stage III disease were included as well.
The aim of our study was to estimate adjuvant treatment effects in stage II colon cancer patients using pooled disease-free survival data from RCTs. Given the dilemma regarding applicability of outcomes from RCTs to the real-world population, our secondary aim was to compare the RCT estimates to estimates based on a national oncology registry.
To estimate treatment effect in stage II colon cancer patients, two approaches were used which we refer to as the “RCT approach” and “real-world data (RWD) approach.” In the RCT approach, we estimated the treatment effect in RCTs using generated patient level data from published survival data. In the RWD approach, treatment effects were estimated in an observational cohort of 1,947 patients by propensity score matching, inverse propensity score weighting and propensity score stratification.
In the RCT approach, patient-level data of 4,489 patients were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio of 0.77 (0.43;1.10) (Figure A) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV (Figure B). In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively.
The RCT data suggests a clinically relevant benefit of adjuvant chemotherapy, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups.