Multiple-Treatments Meta-analysis of Advanced Breast Cancer Therapies
Multiple-Treatments Meta-analysis of Advanced Breast Cancer Therapies
Background: Many systemic nonhormonal regimens have been evaluated across several hundreds of randomized trials in advanced breast cancer. We aimed to quantify the relative merits of these regimens in prolonging survival.
Methods: We performed a systematic review of all trials that compared different regimens involving chemotherapy and/or targeted therapy in advanced breast cancer (1973-2007). Regimens were categorized a priori into different treatment types. We performed multiple-treatments meta-analysis and calculated hazard ratios for each treatment category relative to monotherapy with old agents (ie, regimens not including anthracyclines, anthracenediones, vinorelbine, gemcitabine, capecitabine, taxanes, marimastat, thalidomide, trastuzumab, lapatinib, or bevacizumab).
Results: We identified 370 eligible randomized trials (54,189 patients), of which 172 (31,552 patients) compared different types of treatment. Survival data from 148 comparisons pertaining to 128 of the 172 trials (26,031 patients, 22 different types of treatment) were available for inclusion in the multiple-treatments meta-analysis. Compared with single-agent chemotherapy with old nonanthracycline drugs, anthracycline regimens achieved 22%-33% relative risk reductions in mortality (ie, hazard ratio [HR] for standard-dose anthracycline-based combination: 0.67, 95% credibility interval [CrI] 0.57-0.78). Several newer regimens achieved further benefits (eg, HR [95% CrI] 0.67 [0.55-0.81] for single-drug taxane, 0.64 [0.53-0.78] for combination of anthracyclines with taxane, 0.49 [0.37-0.67] for taxane-based combination with capecitabine or gemcitabine), and similar benefits were seen with several regimens including molecular targeted treatments. Most regimens had very similar efficacy profiles (<5% difference in HR) as first- and subsequent-line therapies.
Conclusions: Stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer. Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles.
The morbidity band mortality impact of breast cancer is very large worldwide and treatment can be challenging. Many pharmacological compounds and administration modalities have been developed for the treatment of advanced breast cancer. Key milestones in the systemic treatments for breast cancer were the introduction of hormonal treatment in the 1940s, combined chemotherapy in 1969, and anthracyclines in 1972. In the 1990s, gemcitabine, vinorelbine, and capecitabine also entered clinical care, followed by taxanes. Additional expensive targeted treatments were introduced in the last decade.
Although progress has been achieved in the field and patients live longer, the relative merits of the many different chemotherapy and targeted treatment regimens are not well understood. Hundreds of trials have been conducted to compare treatments for advanced breast cancer, but because each has compared only two or a few treatments, it is difficult to integrate information on the relative efficacy of all tested regimens. This integration is important because different regimens vary both in cost and in toxicity. Therefore, we performed a comprehensive systematic review of chemotherapy and targeted treatment regimens in advanced breast cancer and evaluated, through a multiple-treatments meta-analysis, the relative merits of the many different regimens used to prolong survival in advanced breast cancer patients. Data were analyzed on all eligible trials as well as separately for first- and subsequent-line treatment.
Background: Many systemic nonhormonal regimens have been evaluated across several hundreds of randomized trials in advanced breast cancer. We aimed to quantify the relative merits of these regimens in prolonging survival.
Methods: We performed a systematic review of all trials that compared different regimens involving chemotherapy and/or targeted therapy in advanced breast cancer (1973-2007). Regimens were categorized a priori into different treatment types. We performed multiple-treatments meta-analysis and calculated hazard ratios for each treatment category relative to monotherapy with old agents (ie, regimens not including anthracyclines, anthracenediones, vinorelbine, gemcitabine, capecitabine, taxanes, marimastat, thalidomide, trastuzumab, lapatinib, or bevacizumab).
Results: We identified 370 eligible randomized trials (54,189 patients), of which 172 (31,552 patients) compared different types of treatment. Survival data from 148 comparisons pertaining to 128 of the 172 trials (26,031 patients, 22 different types of treatment) were available for inclusion in the multiple-treatments meta-analysis. Compared with single-agent chemotherapy with old nonanthracycline drugs, anthracycline regimens achieved 22%-33% relative risk reductions in mortality (ie, hazard ratio [HR] for standard-dose anthracycline-based combination: 0.67, 95% credibility interval [CrI] 0.57-0.78). Several newer regimens achieved further benefits (eg, HR [95% CrI] 0.67 [0.55-0.81] for single-drug taxane, 0.64 [0.53-0.78] for combination of anthracyclines with taxane, 0.49 [0.37-0.67] for taxane-based combination with capecitabine or gemcitabine), and similar benefits were seen with several regimens including molecular targeted treatments. Most regimens had very similar efficacy profiles (<5% difference in HR) as first- and subsequent-line therapies.
Conclusions: Stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer. Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles.
The morbidity band mortality impact of breast cancer is very large worldwide and treatment can be challenging. Many pharmacological compounds and administration modalities have been developed for the treatment of advanced breast cancer. Key milestones in the systemic treatments for breast cancer were the introduction of hormonal treatment in the 1940s, combined chemotherapy in 1969, and anthracyclines in 1972. In the 1990s, gemcitabine, vinorelbine, and capecitabine also entered clinical care, followed by taxanes. Additional expensive targeted treatments were introduced in the last decade.
Although progress has been achieved in the field and patients live longer, the relative merits of the many different chemotherapy and targeted treatment regimens are not well understood. Hundreds of trials have been conducted to compare treatments for advanced breast cancer, but because each has compared only two or a few treatments, it is difficult to integrate information on the relative efficacy of all tested regimens. This integration is important because different regimens vary both in cost and in toxicity. Therefore, we performed a comprehensive systematic review of chemotherapy and targeted treatment regimens in advanced breast cancer and evaluated, through a multiple-treatments meta-analysis, the relative merits of the many different regimens used to prolong survival in advanced breast cancer patients. Data were analyzed on all eligible trials as well as separately for first- and subsequent-line treatment.
