Reporting time-to-event endpoints and response rates in 4 decades of randomized controlled trials in advanced colorectal cancer.
BACKGROUND
Reporting of randomized controlled clinical trials (RCTs) often is suboptimal. Cancer drug trials are complicated further by multiple survival and response endpoints. The authors of this report determined the frequency of reporting of time-to-event endpoints and tumor response outcomes in advanced colorectal cancer and examined the relation between the year of publication and the reported effectiveness of 5-fluorouracil or equivalent agents.


METHODS
A literature search identified 144 RCTs that involved 35,853 patients. The patient characteristics, trial designs, and methods for endpoint reporting were extracted. The clinical effectiveness of 5-fluorouracil or equivalent agents was analyzed in 3 time periods (pre-1990, 1990s, and 2000s) in 28,636 patients.


RESULTS
One hundred twenty-nine trials (90%) reported overall survival (OS) and response rates; whereas time to progression (44%), duration of response (43%), progression-free survival (22%), and time to treatment failure (12%) were reported less frequently. Except for stable and progressive disease, the frequency of reporting of endpoints did not improve over the period studied. The median OS for patients who received 5-fluorouracil or equivalent agents increased significantly (from 9.4 months before 1990 to 13.5 months after 2000). During the same period, the rate of stable disease increased (38.2%, 40.5%, and 45.1% for pre-1990, 1990s, and 2000s, respectively; P = .004); whereas the rate of progressive disease decreased significantly (39.2%, 33.3%, and 27.8%, respectively; P = .002).


CONCLUSIONS
Its likely that the increasing availability of alternative treatments and better supportive care improved OS, whereas the rates of stable and progressive disease altered because of changes in follow-up schedules. Other intermediate endpoints (duration of response and time to progression) remained largely constant over the time course of the current study, making them superior benchmarks for comparison with future studies.
Arkenau
Hendrik-Tobias
HT
Prince of Wales Clinical School and Lowy Cancer Research Center, University of New South Wales, Sydney, New South Wales, Australia.
Nordman
Ina
I
Dobbins
Timothy
T
Ward
Robyn
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D012107:Research Design / Q000639:trends; D013997:Time Factors
D000970:Antineoplastic Agents; D005472:Fluorouracil