Article type
Year
Abstract
Background: Numerous randomized trials have compared different systemic treatment regimens in patients with advanced colorectal cancer. While survival advances have apparently been achieved, the magnitude of these incremental benefits across diverse regimens is less clear.
Objectives: We aimed to present the evolution of the randomized evidence over time as newer regimens were tested. We examined whether there is superior survival with specific regimens versus others and evaluated the magnitude of the benefit.
Methods: We systematically reviewed randomized trials comparing systemic treatment regimens in advanced colorectal cancer. Treatment was categorized by the use or not of 5 fluorouracil-based regimens, irinotecan, oxaliplatin, bevacizumab, and cetuximab. We used multiple-treatment meta-analysis methodology to combine information from direct and indirect comparisons of different categories of chemotherapy, excluding old regimens of 5-fluorouracil without leucovorin. Monte Carlo simulations were used to determine which regimen most improved survival. We performed analyses of all trials and separately for trials that examined first-line treatments.
Results: We found 226 trials (N = 47,671 patients) involving 133 different chemotherapy regimens published in 1967 to 2006. Thirty trials compared different types of chemotherapy, according to our categorization, including 29 comparisons with usable survival information for multiple-treatment meta-analysis (N = 8,043 patients). Several of the most effective regimens had not been compared directly, and thus there was some uncertainty in ranking their effectiveness. There was a 72% probability that the regimen that best prolonged survival is the 5 fluorouracil + leucovorin + irinotecan + bevacizumab combination (HR 0.62, 95% credibility interval [CrI] 0.41 - 0.92 against 5 fluorouracil + leucovorin chemotherapy), but the 95% ranking CrI suggested this regimen is anywhere between 1st and 4th best. When analyses were limited to first line treatment, the same regimen showed a 64% probability that it was the best in prolonging survival (95% CrI, 1st - 3rd). Less definitive benefits were seen with the addition of oxaliplatin (HR 0.84), irinotecan (HR 0.93) irinotecan + oxaliplatin (HR 0.81), or bevacizumab alone (HR 0.79) to 5 fluorouracil + leucovorin.
Conclusions: For patients with expected one year survival on 5 fluorouracil + leucovorin, the benefits translate to two months prolongation with the addition of oxaliplatin and/or irinotecan and seven months prolongation with the addition of irinotecan + bevacizumab. More direct comparisons of the most effective regimens should be encouraged.
Objectives: We aimed to present the evolution of the randomized evidence over time as newer regimens were tested. We examined whether there is superior survival with specific regimens versus others and evaluated the magnitude of the benefit.
Methods: We systematically reviewed randomized trials comparing systemic treatment regimens in advanced colorectal cancer. Treatment was categorized by the use or not of 5 fluorouracil-based regimens, irinotecan, oxaliplatin, bevacizumab, and cetuximab. We used multiple-treatment meta-analysis methodology to combine information from direct and indirect comparisons of different categories of chemotherapy, excluding old regimens of 5-fluorouracil without leucovorin. Monte Carlo simulations were used to determine which regimen most improved survival. We performed analyses of all trials and separately for trials that examined first-line treatments.
Results: We found 226 trials (N = 47,671 patients) involving 133 different chemotherapy regimens published in 1967 to 2006. Thirty trials compared different types of chemotherapy, according to our categorization, including 29 comparisons with usable survival information for multiple-treatment meta-analysis (N = 8,043 patients). Several of the most effective regimens had not been compared directly, and thus there was some uncertainty in ranking their effectiveness. There was a 72% probability that the regimen that best prolonged survival is the 5 fluorouracil + leucovorin + irinotecan + bevacizumab combination (HR 0.62, 95% credibility interval [CrI] 0.41 - 0.92 against 5 fluorouracil + leucovorin chemotherapy), but the 95% ranking CrI suggested this regimen is anywhere between 1st and 4th best. When analyses were limited to first line treatment, the same regimen showed a 64% probability that it was the best in prolonging survival (95% CrI, 1st - 3rd). Less definitive benefits were seen with the addition of oxaliplatin (HR 0.84), irinotecan (HR 0.93) irinotecan + oxaliplatin (HR 0.81), or bevacizumab alone (HR 0.79) to 5 fluorouracil + leucovorin.
Conclusions: For patients with expected one year survival on 5 fluorouracil + leucovorin, the benefits translate to two months prolongation with the addition of oxaliplatin and/or irinotecan and seven months prolongation with the addition of irinotecan + bevacizumab. More direct comparisons of the most effective regimens should be encouraged.