Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis

Background Treatment of advanced colorectal cancer has progressed substanti ally. However, improvements in response rates have not always translated in to significant survival benefits. Doubts have therefore been raised about t he usefulness of tumour response as a clinical endpoint. Methods This meta-analysis was done on individual data from 3791 patients e nrolled in 25 randomised trials of first-line treatment with standard bolus intravenous fluoropyrimidines versus experimental treatments (fluorouracil plus leucovorin, fluorouracil plus methotrexate, fluorouracil continuous i nfusion, or hepatic-arterial infusion of floxuridine), Analyses were by int ention to treat. Findings Compared with bolus fluoropyrimidines, experimental fluoropyrimidi nes led to significantly higher tumour response rates (454 responses among 2031 patients vs 209 among 1760; odds ratio 0.48 [95% CI 0.40-0.57], p<0.00 01) and better survival (1808 deaths among 2031 vs 1580 among 1760; hazard ratio 0.90 [0.84-0.97], p=0.003). The survival benefits could be explained by the higher tumour response rates. However, a treatment that lowered the odds of failure to respond by 50% would be expected to decrease the odds of death by only 6%. In addition, less than half of the variability of the su rvival benefits in the 25 trials could be explained by the variability of t he response benefits in these trials. Interpretation These analyses confirm that an increase in tumour response r ate translates into an increase in overall survival for patients with advan ced colorectal cancer. However, in the context of individual trials, knowle dge that a treatment has benefits on tumour response does not allow accurat e prediction of the ultimate benefit on survival.