A traditional end point for colon adjuvant clinical trials is overall survival, with 5 years demonstrating adequate follow-up.
A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice.
Dr Daniel Sargent and colleagues pooled individual patient data from 18 randomized phase III colon cancer adjuvant clinical trials.
Trials included 43 arms, with a pooled sample size of 20,898 patients.
The primary hypothesis was that disease-free survival, with 3 years of follow-up, is a primary end point that can replace overall survival with 5 years of follow-up.
The research team found that the recurrence rates for years 1 through 5 were 12%, 14%, 8%, 5%, and 3%, respectively.
The team noted that the median time from recurrence to death was 12 months.
|Correlation between 3-year disease-free survival and 5-year overall survival was 0.89|
|Journal of Clinical Oncology|
The researchers observed that 80% of recurrences were in the first 3 years, and 91% of patients with recurrence by 3 years died before 5 years.
Correlation between 3-year disease-free survival and 5-year overall survival was 0.89.
Comparing control versus experimental arms within each trial, the correlation between hazard ratios for disease-free survival and overall survival was 0.92.
The team found that within-trial log-rank testing using both disease-free survival and overall survival provided the same conclusion in 92% of cases.
The researchers reported that formal measures of surrogacy were satisfied.
Dr Sargent's team concluded, “In patients treated on phase III adjuvant colon clinical trials, disease-free survival and overall survival are highly correlated, both within patients and across trials.”
“These results suggest that disease-free survival after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens.”
“However, marginally significant disease-free survival improvements may not translate into significant overall survival benefits.”