Multiple-treatments meta-analysis of chemotherapy and targeted therapies in advanced breast cancer.
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.
Mauri
Davide
D
Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Polyzos
Nikolaos P
NP
Salanti
Georgia
G
Pavlidis
Nicholas
N
Ioannidis
John P A
JP
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D000069287:Capecitabine; D003627:Data Interpretation, Statistical; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D043823:Taxoids; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine