Exploration of time points and cut-off values for early tumour shrinkage to predict survival outcomes of patients with metastatic colorectal cancer treated with first-line chemotherapy using a biexponential model for change in tumour size

BACKGROUND: Several studies reported that early tumour shrinkage (ETS) was associated with overall survival in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy. However, appropriate time point and cut-off value for ETS remain unclear because these varied in previous studies. PATIENTS AND METHODS: We investigated patients with mCRC who received FOLFOX or FOLFIRI with/without molecular-targeted agents as first-line treatment between 2005 and 2014. Using a biexponential model for change in tumour size, a relative change in the sum of the longest diameters of target lesions from baseline was estimated at a certain time point in each individual patient. Associations of survival outcomes with ETS at various time points based on various cut-off values were evaluated by Cox regression analysis with a landmark approach. RESULTS: Among the 67 patients reviewed, the objective response rate was 73.1% (95% CI 62.5% to 83.7%), the median progression-free survival was 10.9 months (95% CI 8.7 to 13.0 months) and the median overall survival was 25.6 months (95% CI 20.1 to 27.3 months). The model for change in tumour size agreed with the actual measured sizes well. Multivariate Cox regression analysis, including performance status, number of metastatic sites and use of targeted agents, showed that ETS at 8 weeks based on a cut-off value of 20% was most significantly associated with overall survival (HR: 0.404, 95% CI 0.231 to 0.707, P=0.0015). CONCLUSION: It is suggested that a time point of 8 weeks and a cut-off value of 20% may be optimal criteria for defining ETS.